Genethon

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Université D'evry-Val-d'essonne

Universitá Degli Studi Di Padova

Association Francaise Contre Les Myopathies

Inserm

Isabelle Richard

Ana Maria Buj Bello

Fedor Svinartchouk

Jérémy Rouillon

Jacques S Beckmann

Dorianna Sandona

Jerome Poupiot

Evelyne Gicquel-Zouida

William Lostal

Natalia Dominguez

Jérôme Poupiot

The present invention relates to an expression system for systemic administration comprising a sequence encoding a protein, said expression system allowing:

Selective gene therapy expression system

The present invention concerns synthetic polynucleotides encoding a human fukutin-related protein (FKRP) wherein the synthetic polynucleotides contain at least a mutation avoiding supplementary transcript(s) generated from frameshift start codon(s). The synthetic polynucleotides are useful, especially for treating a pathology linked to a FKRP deficiency or induced by a defect in &#x3b1;-dystroglycan (&#x3b1;-DG) glycosylation, such as LGMD2I.

Synthetic polynucleotides encoding a human FKRP protein

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 &#x394;F508-CFTR trafficking, and known as CFTR correctors, improved the maturation of several &#x3b1;-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.

Combination treatment of sarcoglycanopathies

The invention relates to a method for prognosing, diagnosing, determining the risk, and monitoring the evolution of a muscular dystrophy. It also relates to a method for evaluating the efficacy of a treatment of a muscular dystrophy in a subject in need thereof.

Methods for diagnosing or monitoring muscular dystrophies

A pharmaceutical composition including at least one epigenome-modifying compound, for a use thereof in the treatment of genetic muscular diseases linked to a conformational disorder of at least one protein, said disorder causing the cellular degradation of the protein.

Use of epigenome-modifying compounds for the treatment of genetic muscular diseases linked to a protein-conformational disorder

Inhibitors of the endoplasmic reticulum associated degradation (ERAD) pathway, particularly inhibitors of mannosidase I, are used for the preparation of a medicinal product intended to treat sarcoglycanopathies.

Drugs for the treatment of sarcogylcanopathies

Inhibitors of the endoplasmic reticulum associated degradation (ERAD) pathway, particularly inhibitors of mannosidase I, are used to treat sarcoglycanopathies.

Drugs for the treatment of sarcoglycanopathies

A nucleic acid sequence comprising: 1) the sequence represented in FIG.; or 2) the sequence represented in FIG.; or 3) a part of the sequence of FIG.with the proviso that it is able to code for a protein having a calcium dependant protease activity involved in a LGMD2; or 4) a sequence derived from a sequence defined in 1), 2) or 3) by substitution, deletion or addition of one or more nucleotides with the proviso that said sequences still codes for said protease.

Growing community of inventors

Corbeil-Essonnes, France

Isabelle Richard