Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
COMBINATION TREATMENT OF SARCOGLYCANOPATHIES
Document Type and Number:
WIPO Patent Application WO/2019/138012
Kind Code:
A1
Abstract:
Sarcoglycanopathies are autosomal recessive diseases caused by mutations in the one of the genes coding for any sarcoglycans (SG). The inventors previously showed that the application of small molecules developed to rescue ∆F508-CFTR trafficking, and known as CFTR correctors, improved the maturation of several α-sarcoglycan mutants that were consequently rescued at the plasma membrane (WO 014086687). Now, the inventors show that some specific CFTR correctors provide additive and even synergic effect when administered in combination.

Inventors:
RICHARD, Isabelle (U951 - GENETHON 1BIS RUE DE L'INTERNATIONALE, Evry, 91002, FR)
SANDONÀ, Dorianna (Dept. of Biomedical Sciences Via U. Bassi, 58/B, Padova, 35131, IT)
Application Number:
EP2019/050585
Publication Date:
July 18, 2019
Filing Date:
January 10, 2019
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) (101 rue de Tolbiac, Paris, Paris, 75013, FR)
UNIVERSITÉ D'EVRY-VAL-D'ESSONNE (23 Boulevard François Mitterrand, Evry, 91000, FR)
GENETHON (1 bis, rue de l'Internationale, Evry, 91000, FR)
UNIVERSITA' DEGLI STUDI DI PADOVA (Via 8 Febbraio, Padova, 35122, IT)
International Classes:
A61K31/427; A61K31/47; A61P21/00
Domestic Patent References:
WO2014086687A12014-06-12
WO2014086687A12014-06-12
WO2014086687A12014-06-12
WO2004111014A12004-12-23
WO2006101740A22006-09-28
Other References:
C. BOINOT ET AL: "Searching for Combinations of Small-Molecule Correctors to Restore F508del-Cystic Fibrosis Transmembrane Conductance Regulator Function and Processing", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 350, no. 3, 26 June 2014 (2014-06-26), pages 624 - 634, XP055483622, DOI: 10.1124/jpet.114.214890
TSUKASA OKIYONEDA ET AL: "Mechanism-based corrector combination restores [Delta]F508-CFTR folding and function", NATURE CHEMICAL BIOLOGY, vol. 9, no. 7, 1 July 2013 (2013-07-01), Basingstoke, pages 444 - 454, XP055483624, ISSN: 1552-4450, DOI: 10.1038/nchembio.1253
CARLOS M. FARINHA ET AL: "Revertants, Low Temperature, and Correctors Reveal the Mechanism of F508del-CFTR Rescue by VX-809 and Suggest Multiple Agents for Full Correction", CHEMISTRY AND BIOLOGY., vol. 20, no. 7, 1 July 2013 (2013-07-01), GB, pages 943 - 955, XP055483627, ISSN: 1074-5521, DOI: 10.1016/j.chembiol.2013.06.004
TIP W LOO ET AL: "Corrector-mediated rescue of misprocessed CFTR mutants can be reduced by the P-glycoprotein drug pump", BIOCHEMICAL PHARMACOLOGY, ELSEVIER, US, vol. 83, no. 3, 18 November 2011 (2011-11-18), pages 345 - 354, XP028349145, ISSN: 0006-2952, [retrieved on 20111128], DOI: 10.1016/J.BCP.2011.11.014
MARCELLO CAROTTI ET AL: "Repairing folding-defective [alpha]-sarcoglycan mutants by CFTR correctors, a potential therapy for limb-girdle muscular dystrophy 2D", HUMAN MOLECULAR GENETICS, vol. 27, no. 6, 16 January 2018 (2018-01-16), gb, pages 969 - 984, XP055483606, ISSN: 0964-6906, DOI: 10.1093/hmg/ddy013
NIGRO, V.; SAVARESE, M.: "Genetic basis of limb-girdle muscular dystrophies: the 2014 update", ACTA MYOL., vol. 33, 2014, pages 1 - 12
TARAKCI, H.; BERGER, J.: "Front. Biosci.", vol. 21, 2016, article "The sarcoglycan complex in skeletal muscle", pages: 744 - 756
SANDONA, D.; BETTO, R.: "Sarcoglycanopathies: molecular pathogenesis and therapeutic prospects", EXPERT REV. MOL. ME., vol. 11, 2009, pages e28, XP055271504, DOI: doi:10.1017/S1462399409001203
KIRSCHNER, J.; LOCHMULLER, H.: "Sarcoglycanopathies", HANDB. CLIN. NEUROL., vol. 101, 2011, pages 141
BARTOLI, M.; GICQUEL, E.; BARRAULT, L.; SOHEILI, T.; MALISSEN, M.; MALISSEN, B.; VINCENT-LACAZE, N.; PEREZ, N.; UDD, B.; DANOS, O.: "Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation", HUM. MOL. GENET., vol. 17, 2008, pages 1214 - 1221
GASTALDELLO, S.; D'ANGELO, S.; FRANZOSO, S.; FANIN, M.; ANGELINI, C.; BETTO, R.; SANDONA, D.: "Inhibition of proteasome activity promotes the correct localization of disease-causing alpha-sarcoglycan mutants in HEK-293 cells constitutively expressing beta-, gamma-, and delta-sarcoglycan", AM. J. PATHOL., vol. 173, 2008, pages 170 - 181
SOHEILI, T.; GICQUEL, E.; POUPIOT, J.; N'GUYEN, L.; LE ROY, F.; BARTOLI, M.; RICHARD, I.: "Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications", HUM. MUTAT., vol. 33, 2012, pages 429 - 439, XP055052557, DOI: doi:10.1002/humu.21659
BIANCHINI, E.; FANIN, M.; MAMCHAOUI, K.; BETTO, R.; SANDONA, D.: "Unveiling the degradative route of the V247M a-sarcoglycan mutant responsible for LGMD-2D", HUM. MOL. GENET., vol. 23, 2014, pages 3746 - 3758
CARRIE, A.; PICCOLO, F.; LETURCQ, F.; DE TOMA, C.; AZIBI, K.; BELDJORD, C.; VALLAT, J.M.; MERLINI, L.; VOIT, T.; SEWRY, C. ET AL.: "Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D", J. MED. GENET., vol. 34, 1997, pages 470 - 475
DUGGAN, D.J.; GOROSPE, J.R.; FANIN, M.; HOFFMAN, E.P.; ANGELINI, C.: "Mutations in the sarcoglycan genes in patients with myopathy", N. ENGL. J. MED., vol. 336, 1997, pages 618 - 624
VAN DER WOERD, W.L.; WICHERS, C.G.; VESTERGAARD, A.L.; ANDERSEN, J.P.; PAULUSMA, C.C.; HOUWEN, R.H.; VAN DE GRAAF, S.F.: "Rescue of defective ATP8B1 trafficking by CFTR correctors as a therapeutic strategy for familial intrahepatic cholestasis", J. HEPATOL., vol. 64, 2016, pages 1339 - 1347, XP029538533, DOI: doi:10.1016/j.jhep.2016.02.001
ZHU, C.H.; MOULY, V.; COOPER, R.N.; MAMCHAOUI, K.; BIGOT, A.; SHAY, J.W.; DI SANTO, J.P.; BUTLER-BROWNE, G.S.; WRIGHT, W.E.: "Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies", AGING CELL, vol. 6, 2007, pages 515 - 523
Attorney, Agent or Firm:
INSERM TRANSFERT (7 rue Watt, Paris, 75013, FR)
Download PDF: