[0001] The present disclosure relates to modification of members of the helminth genus, including helminths commonly known as tapeworms, to achieve certain objectives, and, more particularly, to modify a tapeworm to accomplish medically useful results.

Background

[0002] Tapeworms have been used in their naturally occurring form in certain foreign countries to induce weight loss. One procedure involves a subject intentionally being infested with a tapeworm as found in nature. At a later point in time, the subject ingests a suitable pharmaceutical to cause such tapeworm to die.

[0003] During the time that the tapeworm is resident in the host, the tapeworm may cause unintended and potentially devastating complications. One such complication, particularly devastating, known as cystercercosis, is a disease caused by eggs of the tapeworm being released during its residency within the intestinal tract of the host, and such eggs or resultant cystes then infesting the host's stomach or invading the blood stream through the stomach wall.

[0004] Other potential complications relate to the possibility of eggs being shed in the stool of infected individuals re-infect other humans, generally by the tapeworms shed from one human entering the food chain through livestock intermediaries which pass the tapeworms to other humans.

[0005] Yet another drawback to current techniques is that the worm's activities, while inducing weight-loss, can cause malnutrition.

[0006] The current practice of subsequently taking a drug to kill the parasite may be distasteful to certain people who may otherwise contemplate the treatment. There is likely the possibility that the tapeworm could to grow to as long as thirty feet, which could take hours to expel and thus present a significant unpleasant experience to potential users.

Summary

[0007] A tapeworm modified by suitable techniques is disclosed for use in treating medical conditions or human diseases, such as obesity, asthma, diabetes, or other inflammatory conditions. In one application, the modified tapeworm is introduced in cyst form into a human host in order to encourage weight loss or to treat obesity. Also disclosed are related methods of modifying the tapeworm. Related changes to the physiology of the host are likewise contemplated herein.

Detailed Description

[0008] This disclosure relates to a process for altering the physiology, genetics, or other characteristics of a tapeworm of the Helminth genus. The alteration process may be accomplished in a variety of different manners, including drugs, radiation, or genetic manipulation, for example. It should likewise be appreciated that the tapeworm proceeds through different developmental phases, including egg, cyst, and eventually into adult, worm- form, and that when this disclosure refers to altering, modifying or providing a tapeworm, such reference includes the tapeworm in any of its phases, whether egg, cyst, or adult form unless the context specifically indicates otherwise. As such, the present processes for altering or modifying a tapeworm for use in a parasitic treatment may be distinguished from methods wherein an organism is harvested or assayed to obtain a whole or partial extract of nonliving biological material. That is, the presently described processes, modified tapeworms, and uses thereof, relate to modified and modification of living organisms resulting in a first modified living organism comprising a modified tapeworm, whether in egg, larval or adult form. In various implementations, the first modified living organism is further usable in living form to parasitically treat a second living organism, e.g., a human patient.

[0009] One preferred alteration or manipulation of the tapeworm is one which causes such tapeworm to be sterile, that is, unable to produce functional eggs. For example, the tapeworm may be sterile prior to being received in the host or may be subsequently modified in situ to a sterile state, which may be permanent or temporary. In situ modification of the tapeworm may comprise, for example, ingestion or injection of chemical or biological agent, such as a drug or pharmaceutical, configured to cause or promote the sterile state. In some forms, the tapeworm is rendered sterile via radiation, chemical or biological agents, or modulation of a genetic mechanism or pathway, e.g., resulting in an enzymatic dysfunction or a misregulation of gene expression. In various forms, the tapeworm is genetically modified, recombinantly, for example, or is a member of an artificially created and maintained linage of genetically modified tapeworm of or derived from the Helminth genus comprising sterilized or sterilizable members. Such tapeworms may be modified, for example, to comprise a predetermined susceptibility to radiation, chemical or biological agent, or other trigger resulting in an inability of the tapeworm to produce or release functional or viable eggs. In some forms, the genetically modified linage comprises a transgenic linage comprising a germline modification including, for example, a knockout or conditional knockout directly or indirectly resulting in sterility. In one form, the modification comprises a permanent or transient knockdown effectively imparting permanent or transient sterility. In one form, the knockdown is continuous or triggered by environmental conditions, e.g., chemical or biological, or developmental stages. In certain forms, the tapeworm is modified for readily inducible silencing of genes or products, e.g., regulatory genes, transcription factors, or enzymes, relevant to production or release of functional eggs. In various forms, tapeworms may be modified as described above to produce sterile offspring. Further, in one form, the tapeworm is modified, e.g., by genetic manipulation, to comprise a predetermined susceptibility to radiation, a chemical or biological agent, or otherwise be triggerable to produce sterile offspring. For example, in one implementation, treatment of the host comprises receiving the sterile offspring so produced. As such, the worm's activities would not result in eggs being released within the host, and thus would not risk cystercercosis, or run the risk of infecting others when expelled through stool and progressing into intermediate hosts.

[0010] Another possible alteration or modification of the tapeworm would be to use genetic manipulation, chemical or biological agents, such as drugs or pharmaceuticals, or radiation, as listed previously, to impart developmental programming to the tapeworm. In various forms, the developmental programming is configured to regulate the growth or place temporal limitations on the life expectancy of the tapeworm. For example, in some forms, the tapeworm is modified so that it dies after a set amount of time, grows more slowly, or stops growing after a set length or set amount of time. Further, the tapeworm may be modified such that its rate of growth or development is differentially modulated. For example, in one form, the tapeworm may be programmed to up or down regulate growth at one or more times or periods of development. In one form, the tapeworm is programmed to up or down regulate growth in response to an environmental condition, e.g., a triggering event, in which it resides, such as the presence or absence of a chemical or biological agent. In one form, the genetic modification or other alteration causes the life span or growth limitations to unfold over a desired period of time, such as one year. Whatever period of time is able to be imparted to the tapeworm, the preprogrammed demise of the tapeworm or limitations on its growth or growth rate would reduce the risk of complications associated with ingesting a tapeworm, such as obstruction, and would likewise alleviate the eventual removal or passage of the tapeworm out of the body. [0011] In addition to modification of the tapeworm as described above, additional manners of modification may include use of an intermediate host to cause or trigger modification of the tapeworm. For example, the intermediate host may be induced to cause the release or alteration of the tapeworm, e.g., sterility or developmental programming. In various forms, the intermediate host may be modified or induced to produce, provide, or deliver the trigger to cause or initiate the sterility or developmental programming. As such, the intermediate host may be modified genetically or otherwise to, in-turn, alter or modify the tapeworm. In certain forms, the intermediate host may also be modified or treated with a chemical or biological agent. The chemical or biological agent may comprise a drug configured to cause an alteration or modification of a characteristic of the tapeworm using the machinery of the intermediate host as the vehicle. For example, in one form, the intermediate host comprises a carrier of the tapeworm in a cyst phase. The intermediate host, which may or may not be modified as described above, may be treated with the drug to cause alteration of a characteristic of the tapeworm in a larval phase.

[0012] A suitably modified tapeworm, as described above, may find application in treating human diseases, such as obesity or other weight loss, diabetes, asthma, or other inflammatory diseases. In one implementation, the tapeworm is administered to the host in cyst form, by ingestion or otherwise. After the host receives the cyst, it will be appreciated that the resulting tapeworm, by consuming food within the gastrointestinal system of a host, would induce weight loss in such host, and have any attendant benefits associated with such weight loss, while minimizing some of the aforementioned disadvantages and side effects. The treatment of other human diseases is also contemplated by the administration of the tapeworm in cyst form.

[0013] By assuring that the tapeworm dies after a set period of time or grows more slowly or stops growing, the risk of malnutrition is likewise reduced. As such, the use of such an altered or modified tapeworm could be a valuable tool in treating human diseases, including obesity. It should be understood that the manipulations by drugs, radiation, or genetic manipulations are mentioned in the general sense, and intended to include any of the variety of radiant energies, such as heat, light, sound, etc., any number of pharmaceuticals, chemicals, or other compounds which may affect the characteristics of the tapeworm, and any number of genetic manipulation techniques.

[0014] Still further manipulations may include not only sterility, but sterility under certain conditions (such as when ingested), but also reproductive capabilities (including the ability to produce functional eggs) when outside the host. It is also possible that offspring may be caused to be sterile in some manner by suitable manipulation of the parent tapeworm. Further characteristics of the tapeworm may also be modified, including the ability for the tapeworm to be absorbed by the human host through digestion, ingestion of certain drugs, or through exposure to other aspects of the gastrointestinal environment. Modification of the physical characteristics of the tapeworm may also be accomplished, such as its toughness, tensile strength, or other properties so as to be more readily digested, including sensitivity or receptivity to the host's ingesting certain drugs, and the like.

[0015] A related aspect of the present disclosure is to develop pharmaceuticals or other compositions which manipulate the functions of the host human, such as the gastrointestinal processees, so as to make ingestion of the tapeworm safer of more effective at addressing weight loss issues. As just one example, the modification of the pH of the stomach, such as by eliminating acid, may be found to reduce the risk of developing cystercercosis. Administration of such pharmaceutical may be by injection, ingestion, or any other suitable means.