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Title:
COMPOSITION FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
Document Type and Number:
WIPO Patent Application WO/2021/048440
Kind Code:
A1
Abstract:
The present invention relates to compositions and methods of treatment and/or prevention of diseases and conditions associated with neurodegeneration of a subject. In particular, the present invention relates to compositions comprising at least one human milk oligosaccharide (HMO) and at least one C3-C4-alkane carboxylic acid.

Inventors:
OBERMUELLER-JEVIC UTE (DE)
TOBIN DEREK (NO)
RÜDENAUER STEFAN (DE)
HUSTVEDT SVEIN OLAF (NO)
Application Number:
PCT/EP2020/075651
Publication Date:
March 18, 2021
Filing Date:
September 14, 2020
Export Citation:
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Assignee:
BASF SE (DE)
International Classes:
A23L2/00; A61K31/19; A61K31/702; A61P25/28
Domestic Patent References:
WO2019012461A12019-01-17
WO2019012108A12019-01-17
WO2016029113A12016-02-25
WO2019012108A12019-01-17
Foreign References:
US20180161292A12018-06-14
Other References:
J. BRUCE GERMAN ET AL: "Saturated Fats: A Perspective from Lactation and Milk Composition", LIPIDS, vol. 45, no. 10, 23 July 2010 (2010-07-23), DE, pages 915 - 923, XP055375490, ISSN: 0024-4201, DOI: 10.1007/s11745-010-3445-9
Attorney, Agent or Firm:
BASF IP ASSOCIATION (DE)
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Claims:
Claims:

1. A composition as described in any one of the claims 12 to 20 for use as a medicament, preferably as a medicament for mammals, more preferably for humans.

2. A composition according to any one of claims 12 to 20 for use in the treatment and/or prevention of a neurodegenerative disease, preferably of mammals, more preferably of humans.

3. The composition according to claim 2, wherein the neurodegenerative disease is tauopathy, a synucleinopathy, a TDP-43 proteinopathy, a FUSopathies, a trinucleotide disease, a Prion diseases, a motoneuron disease, a neuroaxonal dystrophy or an unclassified one, in particular a synucleinopathy, more particular Parkinson’s disease.

4. A method for treating a subject having, suspected of having or being at risk of developing a neurodegenerative disease, in particular a neurodegenerative disease as described in claim 2 or 3, comprising administering to the subject an effective amount of a composition according to any one of claims 12 to 20.

5. A nutritional supplement or a functional food comprising a composition as described to any one of claims 12 to 20.

6. The nutritional supplement or the functional food according to claim 5 for use in the treatment and/or prevention of or in the dietary management of a subject having, being suspected or at risk of developing a neurodegenerative disease, preferably of mammals, more preferably of humans.

7. The nutritional supplement or the functional food according to any one of claims 5 to 6, wherein the neurodegenerative disease is tauopathy, a synucleinopathy, a TDP-43 proteinopathy, a FUSopathies, a trinucleotide disease, a Prion diseases, a motoneuron disease, a neuroaxonal dystrophy or an unclassified one, in particular a synucleinopathy, more particular Parkinson’s disease.

8. A method for the dietary management of a subject having, suspected of having or being at risk of developing a disease, in particular a neurodegenerative disease, particuarly Parkinson’s diesease, comprising administering to the subject an effective amount of a composition according to any one of claims 12 to 20 or a nutritional supplement according to any one of claims 5 to 7 or a nutritional food according to any one of claims 5 to 7.

9. A composition according to any one of claims 12 to 20, a composition for use as a medicament according to claim 1 , a composition for use in the treatment or prevention of a neurodegenerative disease according to any one of claims 2 to 3, a nutritional supplement or a functional food according to any one of claims 5 to 7, which is administered to a subject having or being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, wherein the composition according to any one of claims 12 to 20, the composition for use as a medicament according to claim 1 , the composition for use in the treatment or prevention of a neurodegenerative disease according to any one of claims 2 to 3, the nutritional supplement or a functional food according to any one of claims 5 to 7, is administered in an effective amount to the subject in addition to at least one pharmaceutical suitable to treat said neurodegenerative disease, in particular wherein the application rate of the pharmaceutical suitable to treat said neurodegenerative disease is reduced compared to a treatment with said pharmaceutical alone.

10. A method to treat a subject having a neurodegenerative disease, by administering to the subject a) an effective amount of a composition according to any one of claims 12 to 20, a composition for use as a medicament according to claim 1 , a composition for use in the treatment or prevention of a neurodegenerative disease according to any one of claims 2 to 3, a nutritional supplement or a functional food according to any one of claims 5 to 7, or of one of component A and component B as described in any one of claims 12 to 20, and b) an effective amount of at least one pharmaceutical suitable to treat said neurodegenerative disease, wherein the application rate of the at least one pharmaceutical suitable to treat said neurodegenerative disease is reduced compared to a treatment with the at least one pharmaceutical alone.

11. A kit for the pharmaceutical use or dietary management use comprising a first component A being at least one HMO, preferably as described in any one of claims 1 to 9, and a second component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of claims 12 to 20.

12. A composition comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or a derivative thereof.

13. The composition according to claim 12, wherein one of the at least one HMO is 2’- fucosyllactose (2’-FL).

14. The composition according to claim 12 or 13, wherein one of the at least one HMO is 6’- sialyllactose (6’-SL).

15. The composition according to any one of claims 12 to 14, wherein one of the at least one HMO is lacto-N-tetraose (LNT).

16. The composition according to any one of claims 12 to 15, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof.

17. The composition according to any one of claims 12 to 16, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is butyric acid or a derivative thereof.

18. The composition according to any one of claims 12 to 17, wherein the at least one C3-C4- alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof and butyric acid or a derivative thereof.

19. The composition according to any one of claims 12 to 18, wherein the weight to weight ratio of the at least one HMO (component A) : of the at least one C3-C4-alkane carboxylic acid or a derivative thereof (component B) is from 100:1 to 1:100, preferably from 20:1 to 1 :20, more preferably 10:1 to 1:15, particularly 2:1 to 1 :8.

20. The composition according to any one of claims 18 to 19, wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 100: 1 to 1:100, preferably from 20:1 to 1 :20, more preferably from 10:1 to 1 :15, even more preferably 5:1 to 1:20, particularly 2:1 to 1 :8.

Description:
Composition for the treatment of neurodegenerative diseases

Description

The present invention relates to compositions and methods of treatment and/or prevention of diseases and conditions associated with neurodegeneration of a subject. In particular, the pre sent invention relates to compositions comprising at least one human milk oligosaccharide (HMO) and at least one C3-C4-alkane carboxylic acid.

Background of the invention

Neurodegeneration is the progressive loss of structure and/or function of neurons which may lead to the death of the affected neurons. Many neurodegenerative diseases occur as a result of neurodegenerative processes. Neurodegenerative diseases include inter alia Parkinson's dis ease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Although these diseases have different etiologies and symptoms, they all show a pro gressive degeneration and/or death of neuron cells. So, typically the neurodegenerative dis eases are characterized by a slow onset and chronic progression. Notwithstanding the forego ing the process of neurodegeneration is not well understood.

A common feature of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s chorea is the accumulation of mis- folded and/or aggregated proteins. It is hypothesized that the onset and/or progression of brain degeneration may be linked mechanistically to abnormal interactions between brain proteins, which lead to the assembly of the disease proteins into filaments, and the aggregation of these filaments within brain cells or in the extracellular space. The accumulation of large cytotoxic pro tein aggregates triggers proteolytic stress, which, in turn, causes the onset of programmed cell death in vulnerable brain regions. Certain aggregation-prone, disease-specific proteins and se lectively affected brain regions have been identified for certain neurodegenerative diseases (see Table 1).

Table 1 :

The Alzheimer Association estimates that in 2019 5.8 million Americans are living with Alzheimer’s disease. Also, it was reported in 2014 that Parkinson's disease is the second most common neurodegenerative disease in the United States, affecting estimated 1% of the population of the United States over 60 years of age.

Although these neurodegenerative diseases frequently occur and intensive research work is done regarding the treatment thereof, no effective treatment or prevention has yet been identified. Recently WO 2019/012108 reported that a physiologically effective amount of propionic acid and/or butyric acid and/or the physiologically acceptable salts or esters thereof being useful in the prophylactic and/or supporting therapeutic treatment of Parkinson’s disease.

Still, there is an urgent need for compositions being suitable in the treatment and/or prevention of neurodegenerative diseases.

Summary of the invention

Accordingly, the present invention provides in a first aspect a composition comprising i) at least one H MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

Another aspect of the present invention relates to said composition for use in the treatment or prevention of neurodegenerative diseases. In another aspect the present invention relates to methods for treating a subject having, being suspected of having or being at risk of developing a neurodegenerative disease. In a further aspect the present invention relates to a nutritional supplement or a functional food comprising said composition. Another aspect of the present invention is related to the use of said composition as a nutritional supplement or a functional food, in particular in the dietary management of neurodegenerative diseases. In a further aspect the present invention relates to a kit for the pharmaceutical use or dietary management use comprising the components of said composition.

Detailed description of the invention

It has now been found that HMOs can be combined with C3-C4-alkane carboxylic acids or derivatives thereof. Such compositions provide beneficial effects as described herein.

The present invention provides a composition. The composition comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

For the purpose of the present invention, the term “HMO" refers to human milk oligosaccharide(s). These carbohydrates are resistant to enzymatic hydrolysis by digestive enzymes (e.g. pancreatic and/or brush border). In the human breast milk many different kinds of HMOs are found. Each individual HMO is based on a combination of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and/or N-acetylglucosamine with many and varied linkages between them. So far over 130 such structures have been identified in human milk. Almost all of them have a lactose moiety at their reducing end while sialic acid and/or fucose (when present) occupy terminal positions at the non-reducing ends. The HMOs can be acidic (e.g. charged sialic acid containing oligosaccharide) or neutral (e.g. fucosylated oligosaccharide).

In an embodiment of the present invention the HMO is selected from the group of fucosylated oligosaccharides, N-acetylated oligosaccharides and sialylated oligosaccharides.

In an embodiment of the present invention the HMO is a "fucosylated oligosaccharide". These are HMOs having a fucose residue. It has a neutral nature. Some examples are 2'-FL (2'- fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lacto-N-fucopentaose (e.g. lacto-N- fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V), lacto-N-fucohexaose, lacto-N-difucohexaose I, fucosyllacto-N-hexaose, fucosyllacto- N- neohexaose, difucosyllacto-N-hexaose I, difucosyllacto-N-neohexaose II and any combination thereof. In a preferred embodiment the fucosylated oligosaccharide is selected from the group comprising 2’-FL, 3-FL and difucosyllactose (e.g. 2’,2”-DiFL and/or 3,2’-DiFL). In particular, the fucosylated oligosaccharide is 2’-FL.

In another embodiment of the present invention the HMO is a ”N-acetylated oligosaccharide”. The term ”N-acetylated oligosaccharide(s)” encompasses both "N-acetyl-lactosamine" and "oligosaccharide(s) containing N-acetyl-lactosamine". They are neutral oligosaccharides having an N-acetyl-lactosamine residue. Suitable examples are LNT (lacto-N-tetraose), para-lacto-N- neohexaose (para-LNnH), LNnT (lacto-N-neotetraose) or any combination thereof. Other examples are lacto-N-hexaose, lacto-N-neohexaose, para-lacto-N-hexaose, para-lacto-N- neohexaose, lacto-N-octaose, lacto-N- neooctaose, iso- lacto-N-octaose, para- lacto-N-octaose and lacto-N-decaose or any combination thereof. In a preferred embodiment the N-acetylated oligosaccharide is selected from the group of LNT and LNnT.

In another embodiment of the present invention the HMO is a ’’sialylated oligosaccharide". The term ’’sialylated oligosaccharide” encompasses an oligosaccharide having a sialic acid residue. It has an acidic nature. Some examples are 3’-SL (3'-sialyllactose) and 6’-SL (6'-sialyllactose). In a preferred embodiment the sialylated oligosaccharide is 6’-SL.

In another embodiment the HMO is selected from the group comprising 2’-FL, 3-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3,2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL and/or any combination thereof. In particular, the HMO is selected from the group comprising 2’-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT and 6’-SL and/or any combination thereof. Especially the HMO is selected from the group comprising 2’-FL, LNT, LNnT and 6'-SL and/or any combination thereof.

For the purpose of the present invention, the term “C3-C4-alkane carboxylic acid or derivative thereof’ encompasses propionic acid, n-butyric acid and iso-butyric acid (2-methyl propionic acid) as well as derivatives thereof and/or any mixture thereof. Suitable derivatives are salts, esters and amides, in particular physiologically acceptable ones.

Examples for physiologically acceptable salts are alkali salts, like sodium or potassium salts, or alkaline-earth salts, like magnesium or calcium salts, or choline salts. Preferably the physiologically acceptable salts are alkali salts, in particular sodium salts or potassium salts, especially sodium salts.

Examples for physiologically acceptable esters are those derived from C1-C6 alcohols, in particular those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or dihydric C1-C6 alcohols, like those derived from 1,2-ethandiol, or C1-C4 alkoxy substituted monohydric alcohols, like those derived from 2-methoxyethanol, 2-ethoxyethanol or 2-butoxyethanol. Other examples for physiologically acceptable esters are glycerides, like mono-, di-, or triglycerides, in particular mono- or diglycerides. Preferably the physiologically acceptable esters are those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or mono- or diglycerides.

Examples for physiologically acceptable amides are those derived from mono- or di-C1-C6-alkyl amines.

In an embodiment of the present invention the C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid (= free propionic acid) or butyric acid (= free butyric acid) or a mixture thereof.

In another embodiment the C3-C4 alkane carboxylic acid is provided as physiologically acceptable derivative thereof; in particular the derivative is a physiologically acceptable salt, e.g. a sodium salt or potassium salt, or a mixture thereof, or a physiologically acceptable ester, e.g. said ester is derived from C1-C6 alcohols, in particular a mono- or a dihydric C1-C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.

In a further embodiment the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate or sodium butyrate or potassium butyrate or a mixture thereof. Especially, it is sodium propionate or sodium butyrate or a mixture thereof.

In a further embodiment the C3-C4-alkane carboxylic acid or derivative thereof is propionic acid or a derivative thereof, in particular it is a physiologically acceptable salt of propionic acid, especially it is sodium propionate or potassium propionate, or a physiologically acceptable ester of propionic acid, especially methyl propionate or ethyl propionate or propionic acid monoglyceride or propionic acid diglyceride, particularly ethyl propionate or propionic acid monoglyceride. In a particular embodiment the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate. In a further embodiment the C3-C4-alkane carboxylic acid or derivative thereof is butyric acid or a derivative thereof, in particular it is a physiologically acceptable salt of butyric acid, especially it is sodium butyrate or potassium butyrate, or a physiologically acceptable ester of butyric acid, especially methyl butyrate or ethyl butyrate or butyric acid monoglyceride or butyric acid diglyceride, particularly ethyl butyrate or butyric acid monoglyceride. In a particular embodiment the C3-C4-alkane carboxylic acid or derivative thereof is sodium butyrate or potassium butyrate.

In a further embodiment the at least one C3-C4-alkane carboxylic acid or derivative thereof is a mixture of propionic acid and butyric acid or derivatives thereof, in particular it is a mixture of physiologically acceptable salts of propionic acid and butyric acid, especially it is a mixture of sodium propionate and sodium butyrate or a mixture of potassium propionate and potassium butyrate, or a mixture of physiologically acceptable esters of propionic acid and butyric acid, especially a mixture of methyl propionate and methyl butyrate, or a mixture of ethyl propionate and ethyl butyrate, or a mixture of propionic acid monoglyceride and butyric acid monoglyceride, or a mixture of propionic acid diglyceride and butyric acid diglyceride, particularly a mixture of ethyl propionate and ethyl butyrate or a mixture of propionic acid monoglyceride and butyric acid monoglyceride. In a particular embodiment the at least one C3-C4-alkane carboxylic acid or derivative thereof is a mixture of sodium propionate and sodium butyrate or a mixture of potassium propionate and potassium butyrate.

In another embodiment of the present invention the composition comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

In an embodiment of the present invention the composition comprises i) at least one H MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, wherein the ratio of the at least one HMO (component A) and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) is from 100:1 to 1:100, preferably from 20:1 to 1:20, more preferably 10:1 to 1:10, even more preferably from 3:1 to 1 :3, in particular 2:1 to 1 :2.

In another embodiment of the present invention the composition comprises as at least one C3- C4-alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100:1 to 1:100, preferably from 20:1 to 1:20, more preferably from 10:1 to 1:15, even more preferably from 2:1 to 1 :8.

In another embodiment of the present invention the at least one HMO and the at least one C3- C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts. In another embodiment of the present invention the total amount of the at least one HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 1 to 100 wt% of the total composition, preferably from 10 to 100 wt%.

In another embodiment the total amount of the at least one HMO is from 10 to 90 wt% of the total composition, preferably from 20 to 80 wt%, more preferably from 30 to 70 wt%, even more preferably from 40 to 60 wt%. In yet another embodiment the total amount of the at least one HMO is from 5 to 50 wt% of the total composition, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%. In yet another embodiment the total amount of the at least one HMO is from 50 to 95 wt% of the total composition, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.

In another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%. In yet another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%. In yet another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.

In another embodiment of the present invention the composition can further comprise one or more vitamins or related compounds thereto. Examples of vitamins and related compounds thereto include vitamin A (e.g. retinol, retinyl acetate, retinyl palmitate, retinyl stearate, retinyl esters with other long-chain unsaturated fatty acids, retinal, retinoic acid and the like), vitamin B1 (e.g thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate and the like), vitamin B2 (e.g. riboflavine, flavine mononucleotide (FMN), flavine adenine dinucleotide (FAD), lactoflavine, ovoflavine and the like), vitamin B3 (e.g. nicotinic acid, nicotinamide, nicotinamide adenine dinucleotide (NAD), nicotinic acid mononucleotide (NicMN), pyridine-3-carboxylic acid and the like, as well as the vitamin B3-precursor tryptophan), pantothenic acid (e.g. pantothenate, panthenol and the like), vitamin B6 (e.g. pyridoxine, pyridoxal, pyridoxamine, pyridoxine hydrochloride and the like), biotin, folic acid (e.g. folate, folacin, pteroylglutamic acid and the like), vitamin B12 (e.g. cobalamin, methylcobalamin. deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin, adenosylcobalamin and the like), vitamin E (e.g. alpha-, beta-, gamma- and/or delta-tocopherol, alpha-, beta-, gamma- and/or delta-tocopherol acetate, alpha-, beta-, gamma- and/or delta- tocopherol succinate, alpha-, beta-, gamma- and/or delta-tocopherol nicotinate, alpha-, beta-, gamma- and/or delta tocotrienol and the like), vitamin K (e.g. vitamin K1 , phylloquinone, naphthoquinone, vitamin K2, menaquinone-7, vitamin K3, menaquinone-4, menadione, menaquinone-8, menaquinone-8H, menaquinone-9, menaquinone-9H, menaquinone-10, menaquinone-11, menaquinone-12, menaquinone-13 and the like), vitamin C (ascorbic acid), vitamin D (e.g. calciferol, cholecalciferol, 1 ,25-dihydroxyvitamin D, ergocalciferol and the like), and the like and/or mixtures thereof. The presence and amounts of specific vitamins and/or related compounds thereto will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more vitamins or related compounds thereto.

In another embodiment of the present invention the composition can further comprise one or more carotenoids. Examples of carotenoids include astaxanthin, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin and the like (including cis/trans isomers) and/or mixtures thereof.

The presence and amounts of specific carotenoids will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more carotenoids.

In another embodiment of the present invention the composition can further comprise one or more medium-chain fatty acids. These medium-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or alkyl esters. Examples of medium-chain fatty acids include caproic acid, caprylic acid, capric acid, lauric acid and the like and/or mixtures thereof.

The presence and amounts of specific medium chain fatty acids will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more medium-chain fatty acids.

In another embodiment of the present invention the composition can further comprise one or more long-chain fatty acids. These long-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or as alkyl esters. Examples of long chain fatty acids include saturated long chain fatty acids (e.g. myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid and the like and/or mixtures thereof), mono- unsaturated long chain fatty acids (e.g. myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, erucic acid and the like and/or mixtures thereof), polyunsaturated long chain fatty acids (e.g. linoleic acid, linoelaidic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentenoic acid, docosahexaenoic acid and the like and/or mixtures thereof) and/or mixtures thereof. These long chain fatty acids are comprised for example in vegetable oils, single cell oils and marine oils, e.g. fish oil, krill oil and the like.

The presence and amounts of specific long chain fatty acids will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more long-chain fatty acids.

In another embodiment of the present invention the composition can further comprise one or more prebiotics. Examples of prebiotics include water-insoluble fibers (e.g. lignin, cellulose, hemi-cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof), water- soluble fibers (e.g. arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof), other oligosaccharides like xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, isomalto-oligosaccharides and the like and/or mixtures thereof ,in particular water-insoluble fibers (e.g. lignin, cellulose, hemi-cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof), water-soluble fibers (e.g. arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof) and the like and/or mixtures thereof.

The presence and amounts of specific prebiotics will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more prebiotics.

In another embodiment of the present invention the composition can further comprise one or more probiotics. Examples of probiotics optionally present in the composition of the present invention include microorganisms or parts thereof of the family Lactobacillaceae, e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulgaricus, lactobacillus delbrueckii spp. delbrueckii, lactobacillus delbrueckii spp. lactis), lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius and the like), of the genus Bifidobacterium (e.g. the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum and the like), of the genus Pediococcus (e.g. the species pediococcus acidilactici, pediococcus pentosaceus and the like), of the genus Lactococcus (e.g. the species lactococcus lactis (like lactococcus latis spp. cremoris, lactococcus lactis spp. lactic and the like) and of the genus Streptococcus (e.g. the species streptococcus thermophilus and the like) and of the genus Faecalibacterium (e.g. the species faecalibacterium prausnitzii) and of the genus Bacillus (e.g. the species bacillus subtilis) and the like and/or mixtures thereof.

The presence and amounts of specific probiotics will vary depending on the intended use. In another embodiment of the present invention the composition does not comprise one or more probiotics.

In another embodiment of the present invention the composition can further comprise one or more phenolic compounds. Examples of phenolic compounds include monophenols (e.g. apiole, carnosol, carvacrol, dillapiole, rosemarinol and the like), flavonoids (e.g. quercetin, kaempferol, myricetin, fisetin, rutin, isorhamnetin, hesperidin, naringenin, silybin, eriodyctiol, acacetin, apigenin, chrysin, diosmetin, tangeritin, luteolin, catechins like epigallocatechin gallate, theaflavin, thearubigins, proanthocyanidins, pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin and the like), isoflavonoids (e.g. daidzein, genistein, glycitein and the like), aurones, chalconoids, flavonolignans, lignans, phytoestrogens, stilbenoids (e.g. resveratrol, pterostilbene, piceatannol and the like), curcuminoids (e.g. curcumin and the like), tannins, aromatic acids (e.g. salicylic acid, vanillic acid, gallic acid, ellagic acid, tannic acid, caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin and the like), phenylethanoids (e.g. tyrosol, hydroxytyrosol, oleocanthal, oleuropein and the like ), capsaicin, gingerol, alkylresorcinol and the like and/or mixtures thereof.

The presence and amounts of specific phenolic compounds will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more phenolic compounds.

In another embodiment of the present invention the composition can further comprise one or more herbals, e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.

Examples for herbals known from Chinese diets include extracts or powders of hawthorn fruit, wolfberry, spatholobus stem, caterpillar fungus, cloud mushroom, crysanthemum, honeysuckle flower, mulberry leaf, glossy privet fruit, malaytea scurfpea fruit, Cherokee rose fruit, palmleaf raspberry fruit, Chinese magnoliavine fruit, reishi mushroom, ephedra, epimedium, Angelica root, Astragalus root, rhubarb, licorice, morinda root, notoginseng, white peony root, American ginseng, fleeceflower root, kudzu root, rehmannia root, salvia root, Chinese yam, wild buckwheat rhizome, tall gastrodia tuber, golden root, Cassia seed, Coix seed, Dodder seed and the like and/or mixtures thereof.

Examples for herbals known from Indian diets include extracts or powders of Amalaki (Indian gooseberry), Haritaki (chebulic myrobalan), Bibhitaki (beleric), Haldi (turmeric), Tulsi (holy basil), Shigru (moringa), Twak (cinnamon), Yashtimadhu (licorice root), Dhanyaka (coriander), Ashwagandha (winter cherry), Kumkuma (saffron), Manjistha (Indian madder), Brahmi (bacopa), Neem (margosa), Ajwain (Bishop’s weed), Elaichi (cardamom), Shikakai (Acacia concinna), Shatavari (wild asparagus), Jeera (cumin), Guduchi (tinospora) and the like and/or mixtures thereof.

Examples for herbals known from Mediterranean diets include extracts or powders of rosemary, basil, parsley, saffron, thyme, oregano, sage, cilantro, lemon, orange, grape, grapeseed, fig, blueberry, raspberry, strawberry, cherry, fennel, sesame seeds, pine seeds, garlic, onion, ginger root, pepper, chili and the like, olive oil and/or mixtures thereof.

The presence and amounts of specific herbals will vary depending on the intended use.

In another embodiment of the present invention the composition does not comprise one or more herbals.

In another embodiment of the present invention the composition can further comprise one or more minerals. Examples of minerals include such ones comprising calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum and the like and/or mixtures thereof. Minerals are usually added in salt form.

The presence and amounts of specific minerals will vary depending on the intended population.

In another embodiment of the present invention the composition does not comprise one or more minerals.

The compositions of the present invention can be prepared by mixing the at least one HMO, the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally further components e.g. vitamins and related compounds thereto, carotenoids, medium chain fatty acids, long chain fatty acids, prebiotics, probiotics, phenolic compounds, herbals, minerals and the like and/or mixtures thereof, as known in the art.

Furthermore, the present invention provides a composition which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for use as a medicament, preferably as a medicament for mammals.

For the purpose of the present invention, the term ’’mammals” encompasses humans and non human mammals. Examples for non-human mammals are livestock, e.g. sheep, goats, pigs, cattles, horses, camels, llamas and the like, and pets, e.g. cats, dogs and the like.

In a preferred embodiment of the present invention the composition is for use as a medicament for humans.

In another preferred embodiment of the present invention the composition is for use as a medicament for livestock and/or pets. The compositions of the present invention for use as a medicament can be administered orally, enterally or parenterally, preferably orally.

In an embodiment of the present invention the composition for use as a medicament is an orally administrable composition.

In another embodiment of the present invention the composition comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for use as a medicament, preferably as a medicament for humans.

It is understood that the embodiments mentioned for the composition shall be applicable for the compositions for use as a medicament and the specific embodiments thereto.

Furthermore, the present invention provides a composition which comprises i) at least one FI MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the use in the treatment and/or prevention of a neurodegenerative disease, preferably of mammals, more preferably of humans.

For the purpose of the present invention the term ’’treatment” means using an effective therapy or management to alleviate, reduce or cure the disease and/or symptoms thereof, in addition it also includes the stabilization of the disease, in order not to worsen in the course of the disease. In an embodiment of the present invention treatment is understood as using an effective therapy or management to stabilize, alleviate or reduce the disease and/or symptoms thereof.

Within the context of the present invention the term ’’prevention” means an effective therapy or management so that the disease does not de novo develop, manifest and/or symptoms thereof do not occur.

In an embodiment of the present invention the composition is used for the treatment of a neurodegenerative disease.

In another embodiment of the present invention the composition is used for the prevention of a neurodegenerative disease.

For the purpose of the present invention the term ’’neurodegenerative disease” refers to a disease which is caused by the progressive loss of structure and/or function of neurons which may lead to the death of the affected neurons. Typically, neurodegenerative diseases are characterized by a slow onset and chronic progression. In a neurodegenerative disease, a particular part of the brain, spinal cord, or peripheral nerve functionally fails, and the neurons of the dysfunctional region die. The classification of neurodegenerative diseases is often done in an essentially descriptive manner based on the types of misfolded/aggregated proteins, which include tauopathies, e.g. Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, silver grain disease, frontotemporal dementia and parkinsonism of chromosome 17, Morbus Pick and the like; synucleinopathies, e.g. Parkinson's disease, lewy body dementia, multisystem atrophy and the like; TDP-43 proteinopathy, e.g. frontotemporal lobe degeneration with TDP-43 and the like; FUSopathies, e.g. frontotemporal lobe degeneration with FUS, neuronal intermediate filament inclusion disease, basophilic inclusion body disease and the like; trinucleotide diseases, e.g. chorea Fluntington, spinobulbar muscle atrophy type Kennedy, Friedreich's ataxia, spinocerebellar ataxia, dentatorubro-pallidoluysic atrophy and the like; Prion diseases, e.g. Creutzfeldt-Jakob disease, Gerstmann-Scheinker syndrome, deadly familial insomnia, Kuru and the like; motoneuron diseases, e.g. amyotrophic lateral sclerosis, primary lateral sclerosis, spinal muscular atrophy and the like; neuroaxonal dystrophies, e.g. infantile neuroaxonal dystrophy (Seitelberger's disease), neurodegeneration with iron deposition in the brain and the like; and unclassified ones, e.g. frontotemporal lobe degeneration with ubiquitin proteasome system, familial encephalopathy with neuroserpin inclusions, CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome), Mohr-Tranebjaerg syndrome and the like.

In an embodiment of the present invention the composition is for use in the treatment or prevention of a tauopaphy, e.g. Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, silver grain disease, frontotemporal dementia and parkinsonism of chromosome 17, Morbus Pick and the like, preferably for the treatment or prevention of Alzheimer’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of a synucleinopathy, e.g. Parkinson's disease, lewy body dementia, multisystem atrophy and the like; preferably for the treatment or prevention of Parkinson's disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of a trinucleotide disease, e.g. chorea Huntington.

In another embodiment of the present invention the composition is for use in the treatment or prevention of a motoneuron disease, e.g. amyotrophic lateral sclerosis, primary lateral sclerosis, spinal muscular atrophy and the like, preferably for the treatment or prevention of amyotrophic lateral sclerosis.

Human subjects with Parkinson’s disease show often at least one of the following symptoms: hypokinesia, increased muscle tone, abnormal body posture, impaired body posture, tremor, impaired olfaction but also neurophysiologic deficits and certain vegetative/autonomic disturbances.

Hypokinesia may manifest for example in slowing of movement, paucity of facial expression (e.g. mask like face), reduced frequency of blinking and/or speech disturbances (e.g. slow, monotonous, unmodulated speech). In an embodiment of the present invention the composition is for use in the treatment or prevention of hypokinesia, in particular of slowing of movement, paucity of facial expression (e.g. mask like face), reduced frequency of blinking, and/or speech disturbances, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

Increased muscle tone may manifest for example in rigidity. In an embodiment of the present invention the composition is for use in the treatment or prevention of increased muscle tone, in particular of rigidity, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

Abnormal body posture may manifest for example in stooped head and trunk, flexion at the knees. In an embodiment of the present invention the composition is for use in the treatment or prevention of abnormal body posture, in particular of stooped head and trunk and/or flexion at the knees, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of tremor, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of impaired olfaction, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

Neurophysiological deficits may manifest for example in cognitive impairment, bradyphrenia and/or dysexecutive syndrome. In an embodiment of the present invention the composition is for use in the treatment or prevention of cognitive impairment, bradyphrenia and/or dysexecutive syndrome, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In clinical practice the Unified Parkinson’s Disease Rating Scale (UPDRS) has been developed which may at least partly be used or assist in the diagnoses of Parkinson’s disease, e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

Human subjects with Alzheimer’s disease show often at least one of the following symptoms: memory impairment, language problems, personality changes, confusion, hallucinations and delusions, loss of the ability to perform activities of the daily live.

In an embodiment of the present invention the composition is for use in the treatment or prevention of memory impairment, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease. In another embodiment of the present invention the composition is for use in the treatment or prevention of personality changes, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of language problems, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of confusion, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of hallucinations and/or delusions, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the composition is for use in the treatment or prevention of the loss of the ability to perform activities of daily life, e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In clinical practice the Mini-Mental-State-Test (MMSE) has been developed which may at least partly be used or assist in the diagnosis of Alzheimer’s disease.

The compositions of the present invention for use in the treatment or prevention of a neuro degenerative disease, in particular Parkinson’s disease can be administered orally, enterally or parenterally, preferably orally.

In an embodiment of the present invention the composition for use in the treatment or prevention of a neurodegenerative disease, in particular Parkinson’s disease is an orally administrable composition.

In another embodiment of the present invention the composition comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for use in the treatment or prevention of a neurodegenerative disease of a mammal, in particular Parkinson’s disease of a human.

It is understood that the embodiments mentioned for the composition shall be applicable for the compositions for use in the treatment or prevention of a neurodegenerative disease and the specific embodiments thereto. Furthermore, the present invention provides a method to treat a subject having a disease, in particular a neurodegenerative disease, particularly Parkinson’s disease, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular a neuro degenerative disease, particularly Parkinson’s disease, by administering to the subject an effective amount of the composition which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

It is understood that in this method the composition can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components can be administered separately, preferably orally. Furthermore it is understood that in case the composition comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the composition comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that also these can be administered separately, preferably orally.

In an embodiment thereof, the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.

In another embodiment thereof, the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.

In another embodiment thereof, the propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day.

In a further embodiment thereof, the butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.

In another embodiment the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g, preferably the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g, more preferably the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.

In another embodiment the present invention provides a method to treat a subject having a disease, in particular a neurodegenerative disease, particularly Parkinson’s disease, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular a neurodegenerative disease, particularly Parkinson’s disease, by administering to the subject an effective amount of the composition which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

It is understood that the embodiments mentioned for the composition shall be applicable for the use of the composition in this method accordingly and in the specific embodiments thereto.

Furthermore, the present invention provides the use of a composition comprising i) at least one FI MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a medicament, preferably for the treatment or prevention of a neurodegenerative disease, in particular Parkinson’s disease.

In an embodiment the present invention provides the use of a composition comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a medicament, preferably for the treatment or prevention of a neurodegenerative disease, in particular Parkinson’s disease.

It is understood that the embodiments mentioned for the composition shall be applicable for the use of the composition in this use accordingly and in the specific embodiments thereto.

Furthermore, the present invention provides a nutritional supplement comprising a composition which comprises i) at least one FI MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

For the purpose of the present invention the term “nutritional supplement” means a manufactured product intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease. Examples for nutritional supplements include “dietary supplements” and “medical foods”. A dietary supplement is intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, however it needs not to be used under medical supervision. A medical food is also intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, but it is under medical supervision. The terms “medical foods” and “food for special medical purpose” are interchangeable. It is understood that the nutritional supplement can comprise said composition or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one C3-C4- alkane carboxylic acid or derivative(s) thereof and optional further components in separate form.

In an embodiment of the present invention the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease.

In an embodiment thereof, the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.

In another embodiment thereof, the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, , especially from 2.5 to 6.0 g. Preferably, propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day. Preferably butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day. In another embodiment the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6 g, preferably the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g, more preferably the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.

It is understood that in this method the nutritional supplement can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optional further components can be administered separately, preferably orally. Furthermore it is understood that in case the nutritional supplement comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the nutritional supplement comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that also these can be administered separately, preferably orally.

In another embodiment the present invention provides a nutritional supplement comprising a composition which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease.

It is understood that the embodiments mentioned for the composition shall be applicable for the nutritional supplement accordingly and the specific embodiments thereto.

Furthermore, the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, by administering to the subject an effective amount of the nutritional supplement which comprises a composition comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

It is understood that the nutritional supplement can comprise said composition or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one C3-C4- alkane carboxylic acid or derivative(s) thereof’ and optional further components in separate form.

In an embodiment the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, by administering to the subject an effective amount of the nutritional supplement which comprises a composition comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

It is understood that the embodiments mentioned for the composition shall be applicable for the use of the nutritional supplement in this method accordingly and in the specific embodiments thereto.

Both, the medicament (in general and for the respective specific use) and the nutritional supplement (in general and for the respective specific use) of the present invention can be delivered in any suitable format. Formulations suitable for oral administration may be in the form of capsules, tablets, pills, dragees, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, and the like or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia), each comprising a predetermined amount of the at least one HMO, the at least one C3-C4- alkane carboxylic acid or derivative(s) thereof and optional further components. The medicament (in general and for the respective specific use) and/or the nutritional supplement (in general and for the respective specific use) of the present invention may also be administered as a bolus, electuary or paste. It is understood that the active ingredients of said medicament and nutritional supplement can be delivered together in a respective suitable format or that each of component A and component B can be delivered in a respective format or that each of the active ingredients can be delivered in a respective format, or any combination thereof.

In solid dosage forms for oral administration (capsules, tablets, pills, dragees, lozenges, powders, granules, and the like), the desired components of the composition may be mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as acetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; (10) coloring agents; and (11) flavors, such as lemon, orange, apricot, banana, cherry, strawberry, raspberry, blueberry, peppermint, vanilla, chocolate, coffee, cappuccino flavor and the like. In some cases, the compositions may also comprise buffering agents.

In a specific embodiment powders and/or granules can be reconstituted with water or another aqueous liquid prior to consumption.

Furthermore, the present invention provides a functional food comprising a composition which comprises i) at least one H MO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

For the purpose of the present invention the term “functional food” means a food which is fortified with the composition according to the present invention and intended to be used in a diet, in particular of subjects having, being suspected of having or being at risk of developing a disease. The terms “functional food” and “fortified food” are interchangeable.

Examples for foods being suitable for the preparation of functional foods are (1) dairy products e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) bakery products e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) candy products e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) beverage products e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof. It is understood that the functional food can comprise said composition or that the functional food can comprise any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optional further components in separate form.

Furthermore it is understood that in case the composition comprises as the at least one HMO two or more HMOs these can be comprised separately in the functional food or together as composition, and in case composition the comprises as the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof these can be comprised separately in the functional food or together as composition.

In an embodiment of the present invention the functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease.

In an embodiment thereof, the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.

In another embodiment thereof, the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g. Preferably, propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day. Preferably butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day. In another embodiment the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g, preferably the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g, more preferably the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g, and the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.

In another embodiment the present invention provides a functional food comprising a composition which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease. It is understood that the embodiments mentioned for the composition shall be applicable for the functional food accordingly and the specific embodiments thereto.

Furthermore, the present invention provides a method for the dietary management of a subject having, being suspected to have or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, by administering to the subject an effective amount of the functional food which comprises a composition comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

It is understood that the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optional further components can be comprised separately in the functional food or together as composition.

In an embodiment the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, by administering to the subject an effective amount of a functional food which comprises a composition comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

It is understood that the embodiments mentioned for the composition shall be applicable for the use of the functional food in this method accordingly and in the specific embodiments thereto.

The functional food of the present invention can be prepared by known techniques and it can have any suitable type of format such as (1 ) a dairy product e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) a bakery product e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) a candy product e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) a beverage product e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.

Furthermore, it is contemplated herein that the composition, the composition for use as a medicament, the composition for use in the treatment or prevention of a neurodegenerative disease, the nutritional supplement, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, and the functional food, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, respectively, as disclosed herein, can be co-administered to subjects receiving at least one pharmaceutical against said neurodegenerative disease. Examples for pharmaceuticals used in the treatment of Parkinson’s disease are dopamin precursors e.g L-Dopa and the like; non-ergot dopamin agonists e.g. ropinirol, pramipexol, apomorphin, rotigotin, piribedil and the like; ergot dopamin agonists e.g. bromocriptin, pergolid, lisurid, cabergolin and the like; COMT-inhibitors e.g. entacapon, tolcapon and the like; NMDA-antagonists e.g. amantadin, budipin and the like; MOA-beta-inhibitors e.g. selegilin, rasagilin and the like; anticholinergica e.g. biperiden and the like; and/or mixtures thereof, in particular dopamin precursors, e.g. L-Dopa and the like.

Furthermore, the present invention provides a method to treat a subject having a neurodegenerative disease, by administering to the subject a) an effective amount of a composition, a composition for use as a medicament, a composition for use in the treatment or prevention of a neurodegenerative disease, a nutritional supplement or a functional food, which comprises i) at least one HMO, and/or ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and b) an effective amount of at least one pharmaceutical suitable to treat said neurodegenerative disease, wherein the application rate of the at least one pharmaceutical suitable to treat said neurodegenerative disease is reduced compared to a treatment with the at least one pharmaceutical alone.

In an embodiment thereof the neurodegenerative disease is Parkinson’s disease and the pharmaceutical is L-Dopa. In particular, the composition, the composition for use as a medicament, the composition for use in the treatment or prevention of Parkinson’s disease, the nutritional supplement, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, or a functional food, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, or used in said method comprises 2’-FL and/or propionic acid and/or butyric acid or derivative(s) thereof, preferably 2’-FL, sodium propionate and sodium butyrate.

In another embodiment thereof the neurodegenerative disease is Parkinson’s disease and the pharmaceutical is L-Dopa. In particular, the composition, the composition for use as a medicament, the composition for use in the treatment or prevention of Parkinson’s disease, the nutritional supplement, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, or a functional food, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, used in said method comprises only 2’-FL as active ingredient of part a) above.

In another embodiment thereof the neurodegenerative disease is Parkinson’s disease and the pharmaceutical is L-Dopa. In particular, the composition, the composition for use as a medicament, the composition for use in the treatment or prevention of Parkinson’s disease, the nutritional supplement, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, or a functional food, in particular for use in the dietary management of subjects having, being suspected or being at risk developing a neurodegenerative disease, used in said method comprises 2’ FL and either propionic acid or a derivative thereof or butyric acid or a derivative thereof.

Furthermore, the present invention provides a composition comprising a) i) at least one FIMO, and/or ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and b) an effective amount of at least one pharmaceutical, in particular for use as a medicament, especially for use in the treatment or prevention for a neurodegenerative disease.

In an embodiment thereof the present invention provides a composition comprising a) i) as component A 2’-FL, and/or ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate, and b) levodopa in a pharmaceutical effective amount, in particular for use as a medicament, especially for use in the treatment or prevention for a neurodegenerative disease, especially Parkinson disease.

In an embodiment thereof the present invention provides a composition comprising a) as component A at least one HMO, preferably 2’-FL, and b) levodopa in a pharmaceutical effective amount, without any C3-C4 C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use as a medicament, especially for use in the treatment or prevention for a neurodegenerative disease, especially Parkinson disease.

It is understood that the embodiments mentioned for the components and for the diseases and the symptoms mentioned above shall apply here to.

In a preferred embodiment the daily application rate of levodopa is from 0.1 to 2.0 g, in particular from 0.3 to 1.0 g.

In an embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of, or in the dietary management of a subject with a tauopaphy, e.g. Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, silver grain disease, frontotemporal dementia and parkinsonism of chromosome 17, Morbus Pick and the like, preferably for the treatment or prevention of Alzheimer’s disease. In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of, or in the dietary management of a subject with a synucleinopathy, e.g. Parkinson's disease, lewy body dementia, multisystem atrophy and the like; preferably for the treatment or prevention of, or in the dietary management of a subject with Parkinson's disease, in particular in the dietary management of a subject with Parkinson disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of, or in the dietary management of a subject with a trinucleotide diseases, e.g. chorea Huntington.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of, or in the dietary management of a subject with a motoneuron diseases, e.g. amyotrophic lateral sclerosis, primary lateral sclerosis, spinal muscular atrophy and the like; preferably for the treatment or prevention of, or in the dietary management of a subject with amyotrophic lateral sclerosis, in particular in the dietary management of a subject with amyotrophic lateral sclerosis.

In an embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of memory impairment e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease, or in the dietary management of a subject with memory impairment, of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of personality changes e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease or in the dietary management of a subject with personality changes, of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the medicament, the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of language problems e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease or in the dietary management of a subject with language problems, of a subject having or being suspected or at risk of developing Alzheimer’s disease. In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of confusion e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease or in the dietary management of a subject with confusion, of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of hallucinations and/or delusions e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease or in the dietary management of a subject with hallucinations and/or delusions, of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of the loss of the ability to perform activities of the daily life e.g. of a subject having or being suspected or at risk of developing Alzheimer’s disease or in the dietary management of a subject with hallucinations and/or delusions, of a subject having or being suspected or at risk of developing Alzheimer’s disease.

In an embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of hypokinesia, in particular of slowing of movement, paucity of facial expression (e.g. mask like face), reduced frequency of blinking, and/or speech disturbances e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with hypokinesia, in particular of slowing of movement, paucity of facial expression (e.g. mask like face), reduced frequency of blinking, and/or speech disturbances e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In an embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of increased muscle tone, in particular of rigidity e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with increased muscle tone, in particular of rigidity e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In an embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of abnormal body posture, in particular of stooped head and trunk and/or flexion at the knees e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with abnormal body posture, in particular of stooped head and trunk and/or flexion at the knees e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of tremor e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with tremor of a subject having or being suspected or at risk of developing Parkinson’s disease.

In another embodiment of the present invention the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of impaired olfaction e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with impaired olfaction of a subject having or being suspected or at risk of developing Parkinson’s disease.

In an embodiment of the present invention the medicament, the nutritional supplement or the functional food is for use in the treatment or prevention of or dietary management of a subject with, in particular in the treatment or prevention of in cognitive impairment, bradyphrenia and/or dysexecutive syndrome e.g. of a subject having or being suspected or at risk of developing Parkinson’s disease or in the dietary management of a subject with cognitive impairment of a subject having or being suspected or at risk of developing Parkinson’s disease.

Furthermore, the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising at least one HMO and a second component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

In an embodiment the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, and a second component comprising propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

In another embodiment the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, a second component comprising propionic acid or derivative(s) thereof, preferably sodium propionate, and a third component comprising butyric acid or derivative(s) thereof, preferably sodium butyrate.

It is understood that the embodiments mentioned for the components A and B shall be applicable for the kit accordingly and in the specific embodiments thereto.

Furthermore, the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising at least one FI MO, and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of a neurodegenerative disease, in particular Parkinson disease, and optionally a third component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.

In an embodiment the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, a second component comprising levodopa and optionally a third component comprising propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.

In another embodiment the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL and a second component comprising levodopa, without any C3-C4-alkane carboxylic acid or derivative(s) thereof.

It is understood that the embodiments mentioned for the components A and B and the diseases shall be applicable for the kit accordingly and in the specific embodiments thereto.

Within the context of the present invention, the term "butyric acid" denotes n-butyric acid and the term “butyrate” denotes n-butyrate. Also within the content of the present invention, the term ”at least one FI MO” is interchangeable with the term ’’component A”, and the term ”at least one C3-C4-alkane carboxylic acid or a derivative thereof’ is interchangeable with the term “component B”.

Within the context of the present application, it is noted that in case the composition comprises several components that these can also be administered separately. Flowever, this means that such components can be administered together or separately, as the case may be.

Also, within the context of the present invention, ratios given are weight to weight ratios unless stated otherwise. In addition, in the context of the invention, the terms "comprising" or "comprises" do not exclude other possible elements. The composition of the present invention, including the embodiments described herein, can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs. The terminology as set forth herein is for description of the embodiments only and should not be construed as limiting the disclosure as a whole. Furthermore, as used in the description and the appended claims, the singular forms "a", "an", and "the" are inclusive of their plural forms, and the other way around, unless the context clearly indicates otherwise. It is to be understood that the embodiments of the subject matter of the invention can be applied in the specific context but also in other combinations, without leaving the scope of the invention. E.g. it is understood that the embodiments mentioned for the composition of the present invention also apply for composition for use as a medicament, etc.

In the following specific embodiments of the present invention are described. 1. A composition comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or a derivative thereof.

2. The composition according to embodiment 1 , wherein one of the at least one HMO’s is a fucosylated oligosaccharide.

3. The composition according to embodiment 1 or 2, wherein one of the at least one HMO is 2’-fucosyllactose (2’-FL).

4. The composition according to any one of embodiments 1 to 3, wherein one of the at least one HMO’s is a sialylated oligosaccharide.

5. The composition according to any one of embodiments embodiment 1 to 4, wherein one of the at least one HMO is 6’-sialyllactose (6’-SL).

6. The composition according to any one of embodiments 1 to 5, wherein one of the at least one HMO’s is a N-acetylated oligosaccharide oligosaccharide.

7. The composition according to any one of embodiments 1 to 6, wherein one of the at least one HMO is lacto-N-tetraose (LNT).

8. The composition according to any one of embodiments 1 to 7, wherein the at least one HMO is one or more HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyl- lactose (2’,2”-DiFL and/or 3,2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.

9. The composition according to any one of embodiments 1 to 8, wherein the at least one HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyllactose (2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.

10. The composition according to any one of embodiments 1 to 9, wherein the at least one HMO is one, two or three HMOs selected from the group consisting of 2’-FL, LNT, LNnT, 3’-SL and 6’-SL.

11. The composition according to any one of embodiments 1 to 9, wherein the at least one HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 2’,2”-DiFL and 3,2’-DiFL.

12. The composition according to any one of embodiments 1 to 11 wherein the at least one HMO is 2’-FL. 13. The composition according to any one of embodiments 1 to 12, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof.

14. The composition according to any one of embodiments 1 to 13, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt or ester of propionic acid.

15. The composition according to any one of embodiments 1 to 14, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid.

16. The composition according to any one of embodiments 1 to 15, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid.

17. The composition according to any one of embodiments 1 to 16 wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate.

18. The composition according to any one of embodiments 1 to 14, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid.

19. The composition according to any one of embodiments 1 to 18, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is butyric acid or a derivative thereof.

20. The composition according to any one of embodiments 1 to 19, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt or ester of butyric acid.

21. The composition according to any one of embodiments 1 to 20, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of butyric acid.

22. The composition according to any one of embodiments 1 to 21 , wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium salt of butyric acid.

23. The composition according to any one of embodiments 1 to 22 wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium butyrate. 24. The composition according to any one of embodiments 1 to 20, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of butyric acid.

25. The composition according to any one of embodiments 1 to 24, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof and butyric acid or a derivative thereof.

26. The composition according to any one of embodiments 1 to 25, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt of propionic acid and physiologically acceptable salt of butyric acid.

27. The composition according to any one of embodiments 1 to 26, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid and an alkali salt or an alkaline earth salt of butyric acid.

28. The composition according to any one of embodiments 1 to 27, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid and a sodium or potassium salt of butyric acid.

29. The composition according to any one of embodiments 1 to 28 wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate and sodium or potassium butyrate.

30. The composition according to any one of embodiments 1 to 25, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable ester of propionic acid and a physiologically acceptable ester of butyric acid.

31. The composition according to any one of embodiments 1 to 30, wherein the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid and a C1-C6 alkyl ester or a mono- or diglyceride of butyric acid.

32. The composition according to any one of embodiments 1 to 31 , wherein the weight to weight ratio of the at least one HMO (component A) : the at least one C3-C4 alkane carboxylic acid or a derivative thereof (component B) is from 100:1 to 1 :100.

33. The composition according to any one of embodiments 1 to 32, wherein the weight to weight ratio of (component A) : (component B) is from 20:1 to 1 :20, preferably from 10:1 to 1 :10, more preferably from 3:1 to 1:3, in particular from 2:1 to 1 :2. 34. The composition according to any one of embodiments 25 to 33, wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 100:1 to 1:100.

35. The composition according to any one of embodiments 25 to 34, wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 20:1 to 1:20, preferably from 10:1 to 1:15, more preferably from 2:1 to 1 :8.

36. The composition according to any one of embodiments 1 to 35, wherein the at least one HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.

37. The composition according to any one of embodiments 1 to 36, wherein the total amount of the at least one HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 1 to 100 wt% of the total composition, preferably from 10 to 100 wt%.

38. The composition according to any one of embodiments 1 to 37, wherein the total amount of the at least one H MO is from 10 to 90 wt% of the total composition, preferably from 20 to 80 wt%, more preferably from 30 to 70 wt%, even more preferably from 40 to 60 wt%.

39. The composition according to any one of embodiments 1 to 37, wherein the total amount of the at least one HMO is from 5 to 50 wt% of the total composition, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%.

40. The composition according to any one of embodiments 1 to 37, wherein the total amount of the at least one HMO is from 50 to 95 wt% of the total composition, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.

41. The composition according to any one of embodiments 1 to 40, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%.

42. The composition according to any one of embodiments 1 to 40, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.

43. The composition according to any one of embodiments 1 to 40, wherein the total amount of at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%. 44. The composition according to any one of embodiments 1 to 43, wherein the composition further comprises one or more vitamins or related compounds thereto.

45. A composition according to embodiment 44, wherein the one or more vitamins or related compounds thereto are selected from the group of vitamin A, vitamin B1, vitamin B2, vitamin B3, pantothenic acid, vitamin B6, biotin, folic acid, vitamin B12, vitamin E, vitamin K, vitamin C and vitamin D, or related compounds thereto and/or mixtures thereof.

46. The composition according to any one of embodiments 1 to 45, wherein the composition further comprises one or more carotenoids.

47. The composition according to embodiment 46, wherein the one or more carotenoids are selected from the group of astaxanthin, alpha-carotene, beta-carotene, beta- cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin (including cis/trans isomers) and/or mixtures thereof.

48. The composition according to any one of embodiments 1 to 47, wherein the composition further comprises one or more medium-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.

49. The composition according to embodiment 48, wherein the one or more medium chain fatty acids are selected from the group of caproic acid, caprylic acid, capric acid, lauric acid and/or mixtures.

50. The composition according to any one of embodiments 1 to 49, wherein the composition further comprises one or more long-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.

51. The composition according to embodiment 50, wherein the one or more long chain fatty acids are selected from the group of saturated long chain fatty acids, mono-unsaturated long chain fatty acids, polyunsaturated long chain fatty acids and/or mixtures thereof.

52. The composition according to any one of embodiments 1 to 51 , wherein the composition further comprises one or more prebiotics.

53. The composition according to embodiment 52, wherein the one or more prebiotics are selected from the group of water-insoluble fibers, water-soluble fibers and/or mixtures thereof.

54. The composition according to any one of embodiments 1 to 53, wherein the composition further comprises one or more probiotics. 55. The composition according to embodiment 54, wherein the one or more probiotics are selected from the group of the family Lactobacilaceae, preferably of the genus Lactobacillus, in particular of the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius, of the genus Bifidobacterium, in particular of the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum, of the genus Pediococcus, in particualar of the species pediococcus acidilactici, pediococcus pentosaceus, of the genus Lactococcus, in particular of the species lactococcus lactis, of the genus Streptococcus, in particular of the species streptococcus thermophilus, of the genus Faecalibacterium, in particular of the species faecalibacterium prausnitzii, of the genus Bacillus, in particular of the species bacillus subtilis, and/or mixtures thereof.

56. The composition according to any one of embodiments 1 to 55, wherein the composition further comprises one or more phenolic compounds.

57. The composition according to embodiment 56, wherein the one or more phenolic compounds are selected from the group of monophenols, flavonoids, isoflavonoids, aurones, chalconoids, flavonolignans, lignans, phytoestrogens, stilbenoids, piceatannol, curcuminoids, tannins, aromatic acids, phenylethanoids, capsaicin, gingerol, alkylresorcinol and/or mixtures thereof.

58. The composition according to any one of embodiments 1 to 57, wherein the composition further comprises one or more herbals.

59. The composition according to embodiment 58, wherein the one or more herbals are selected from herbals known from Chinese diets, Indian diets, Mediterranean diets and/or mixtures thereof.

60. The composition according to any one of embodiments 1 to 59, wherein the composition further comprises one or more minerals.

61. A composition as described in any one of the embodiments 1 to 60 for use as a medicament, preferably as a medicament for mammals, more preferably for humans.

62. A composition as described in any one of embodiments 1 to 60 for use in the treatment and/or prevention of a neurodegenerative disease, preferably of mammals, more preferably of humans.

63. The composition according to embodiment 62, wherein the neurodegenerative disease is a tauopathy, a synucleinopathy, a TDP-43 proteinopathy, a FUSopathies, a trinucleotide disease, a Prion diseases, a motoneuron disease, a neuroaxonal dystrophy or an unclassified one.

64. The composition according to any one of embodiments 62 to 63, wherein the neurodegenerative disease is a tauopathy, in particular Alzheimer’s disease.

65. The composition according to any one of embodiments 62 to 63, wherein the neurodegenerative disease is a synucleinopathy, in particular Parkinson’s disease.

66. The composition according to any one of embodiments 62 to 63, wherein the neurodegenerative disease is a trinucleotide disease, in particular Chorea Huntington.

67. The composition according to any one of embodiments 62 to 63, wherein the neurodegenerative disease is a motoneuron disease, in particular amyotrophic lateral sclerosis.

68. A composition as described in any one of embodiments 1 to 60 for use in the treatment or prevention of hypokinesia, increased muscle tone, abnormal body posture, impaired body posture, tremor, impaired olfaction, neurophysiologic deficits and/or vegetative/autonomic disturbances of subjects, in particular humans, having or being suspected or at risk of developing Parkinson’s disease.

69. A composition as described in any one of embodiments 1 to 60 for use in the treatment or prevention of memory impairment, language problems, personality changes, confusion, hallucinations and delusions, loss of the ability to perform activities of the daily live of subjects, in particular humans, having or being suspected or at risk of developing Alzheimer’s disease.

70. The composition according to any one of embodiments 61 to 69, wherein the composition is an orally administrable composition.

71. A method for treating a subject having, suspected of having or being at risk of developing a disease, in particular a neurodegenerative disease, particularly Parkinson’s disease, comprising administering to the subject an effective amount of a composition according to any one of embodiments 1 to 60.

72. The method according to embodiment 71 , wherein the application rate of the at least one HMO is from 0.1 to 20.0 g/day, preferably from 2.0 to 10.0 g/day.

73. The method according to any one of embodiments 71 to 72, wherein the application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g/day, preferably from 2.0 to 8.0 g/day. 74. The method according to any one of embodiments 71 to 73, wherein one of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is propionic acid or a derivative thereof and is applied at a rate from 0.1 to 6.0 g/day.

75. The method according to any one of embodiments 71 to 74, wherein one of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is butyric acid and/or a derivative thereof and is applied at a rate from 0.1 to 9.0 g/day.

76. The method according to any one of embodiments 71 to 75, wherein the at least one C3- C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day.

77. The method according to any one of embodiments 71 to 76, wherein the composition is administered orally.

78. A nutritional supplement or a functional food comprising a composition according to any one of embodiments 1 to 60.

79. The nutritional supplement or the functional food according to embodiment 78 for use in the treatment and/or prevention of a neurodegenerative disease, or the dietary management of a subject having, being suspected or at risk of developing a neurodegenerative disease, preferably of mammals, more preferably of humans.

80. The nutritional supplement or the functional food according to any one of embodiments 78 to 79, wherein the neurodegenerative disease is a tauopathy, a synucleinopathy, a TDP- 43 proteinopathy, a FUSopathies, a trinucleotide disease, a Prion diseases, a motoneuron disease, a neuroaxonal dystrophy or an unclassified one.

81. The nutritional supplement or the functional food according to any one of embodiments 78 to 80, wherein the neurodegenerative disease is a tauopathy, in particular Alzheimer’s disease.

82. The nutritional supplement or the functional food according to any one of embodiments 78 to 80, wherein the neurodegenerative disease is a synucleinopathy, in particular Parkinson’s disease.

83. The nutritional supplement or the functional food according to any one of embodiments 78 to 80, wherein the neurodegenerative disease is a trinucleotide disease, in particular Chorea Huntington. 84. The nutritional supplement or the functional food according to any one of embodiments 78 to 80, wherein the neurodegenerative disease is a motoneuron disease, in particular amyotrophic lateral sclerosis.

85. The nutritional supplement or the functional food according to embodiment 78 to 79 for use in the treatment or prevention of or the dietary management of a subject having, being suspected or at risk of developing hypokinesia, increased muscle tone, abnormal body posture, impaired body posture, tremor, impaired olfaction, neurophysiologic deficits and/or vegetative/autonomic disturbances of subjects, in particular humans, having or being suspected or at risk of developing Parkinson’s disease.

86. The nutritional supplement or the functional food according to embodiment 78 to 79 for use in the treatment or prevention of or the dietary management of a subject having, being suspected or at risk of developing memory impairment, language problems, personality changes, confusion, hallucinations and delusions, loss of the ability to perform activities of the daily life of subjects, in particular humans, having or being suspected or at risk of developing Alzheimer’s disease.

87. A method for the dietary management of a subject having, suspected of having or being at risk of developing a disease, in particular a neurodegenerative disease, particularly Parkinson’s disease, comprising administering to the subject an effective amount of a composition according to any one of embodiments 1 to 60 or a nutritional supplement according to embodiment 78 to 79 or a nutritional food according to embodiment 78 to 79.

88. The method according to embodiment 87, wherein the application rate of the at least one HMO is from 0.1 to 20.0 g/day, preferably from 1.0 to 15.0 g/day, more preferably from 2.0 to 10.0 g/day, in particular from 2.5 to 5.0 g/day.

89. The method according to any one of embodiments 87 to 88, wherein the application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g/day, preferably from 1.0 to 9.0 g/day, more preferably from 1.2 to 9.0 g/day, in particular from 2.0 to 8.0 g/day, especially from 2.5 to 6.0 g/day .

90. The method according to any one of embodiments 87 to 89, wherein one of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is propionic acid or a derivative thereof and is applied at a rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day.

91. The method according to any one of embodiments 87 to 90, wherein one of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is butyric acid and/or a derivative thereof and is applied at a rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day. 92. The method according to any one of embodiments 87 to 91 , wherein the at least one C3- C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day, preferably the application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g/day, more preferably the application rate of propionic acid and/or a derivative thereof is from

1.0 to 3.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g/day.

93. The method according to any one of embodiments 87 to 92, wherein the nutritional supplement or the nutritional food is administered orally.

94. A composition according to any one of embodiments 1 to 60, a composition for use as a medicament according to embodiment 61 , a composition for use in the treatment or prevention of a neurodegenerative disease according to any one of embodiments 62 to 70, a nutritional supplement or a functional food according to embodiment 78 to 79, which is administered to a subject having or being suspected of having or being at risk of developing a neurodegenerative disease, in particular Parkinson’s disease, wherein the composition according to any one of embodiments 1 to 60, the composition for use as a medicament according to embodiment 61 , the composition for use in the treatment or prevention of a neurodegenerative disease according to any one of embodiments 62 to 70, the nutritional supplement or a functional food according to embodiment 78 to 79 is administered to the subject in addition to at least one pharmaceutical suitable to treat said neurodegenerative disease, in particular wherein the application rate of the pharmaceutical suitable to treat said neurodegenerative disease is reduced compared to a treatment with said pharmaceutical alone.

95. A method to treat a subject having a neurodegenerative disease, by administering to the subject a) an effective amount of a composition according to any one of embodiments 1 to 60, a composition for use as a medicament according to embodiment 61 , a composition for use in the treatment or prevention of a neurodegenerative disease according to any one of embodiments 62 to 70, a nutritional supplement or a functional food according to embodiment 78 to 79, or with only one of component A and component B as described in any one of embodiments 1 to 60, and b) an effective amount of at least one pharmaceutical suitable to treat said neurodegenerative disease, wherein the application rate of the at least one pharmaceutical suitable to treat said neurodegenerative disease is reduced compared to a treatment with the at least one pharmaceutical alone. 96. A method according to embodiment 95, wherein the neurodegenerative disease is Parkinson’s disease and wherein the at least one pharmaceutical suitable to treat said neurodegenerative disease is selcted from the group of dopamin precursors, non-ergot dopamin agonists, ergot dopamin agonists, COMT-inhibitors, NMDA-antagonists, MOA- beta-inhibitors, anticholinergica and/or mixtures thereof, preferably L-Dopa.

97. Use of the composition as defined in any one of embodiments 1 to 60 as a nutritional supplement for the dietary management of a neurodegenerative disease.

98. A kit for the pharmaceutical use or dietary management use comprising a first component A being at least one HMO, preferably as described in any one of embodiments 1 to 60, and a second component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of embodiments 1 to 60.

Examples

The following examples illustrate certain exemplary embodiments of the subject matter of the present invention as detailed above. The Examples are given solely for the purpose of illustration and are not to be construed as limitation.

Example 1 : Randomized, double-blind study with patients with Parkinson Disease

The study was performed with seventytwo patients with diagnosed Morbus Parkinson in a double-blind, randomized clinical trial.

Patients meet the below criteria to be included in the trial: between 18 and 90 years of age, primary Parkinson syndrome, moderate disease severity (UPDRS III 8 or lower, stable daily dosage of 500 - 850 mg per day levodopa), completely oriented regarding time, place and person, independent mobility without, with one-sided or two-sided walking aid. and did not meet any of the following exclusion criteria: bad general condition, pregnancy,

- serious accompanying illness or organ dysfunction (e. g. Heart Faillure NYHA grade III- IV, severe respiratoryfailure (e.g. with calm dyspnea), irreversible multiple organ failure, sepsis, acute viral hepatitis,

- serious disease of the gastrointestinal tract, malignancies (actual or in actual follow-up, aftercare),

- therapy with immunesuppresiva in the last 6 months (e.g. with mitoxantron, azathioprin, cyclophosphamid),

- vegan eating habits.

The patients were grouped in three groups, in one group each of the patients received 1260 mg per day sodium propionate and 2550 mg per day sodium butyrate, in another group each of the patients received 3250 mg per day 2’-FL, and in the third group each of the patients received 1260 mg per day sodium propionate, 2550 mg per day sodium butyrate and 3250 mg per day 2’-FL, for the duration of the trial.

During the trial the individual dosage of each of the patients with levodopa was readjusted if possible and/or necessary. At the beginning of the trial, after 12 weeks and after 24 weeks the UPDRS III score and the dosage of levodopa of each patient was determined.

After 24 weeks in was observed that the daily dosage of levodopa could be reduced in each treatment group, and in particular in the treatment group receiving a combination of sodium propionate & sodium butyrate and 2’-FL (treatment group propionate/butyrate: about 24 % reduction; treatment group 2’-FL: about 20 %; treatment group propionate/butyrate + 2’-FL: about 28 %), and in addition the respective UPDRS III store was improved.