Abstract: Gene therapy for treating dysferlinopathy. More particularly, a polynucleotide sequence including several domains of dysferlin, or functional variants thereof, and a viral vector for gene therapy including at least a polynucleotide sequence, which includes exon 40a of the coding sequence of dysferlin. Also, a pharmaceutical composition including the viral vector.

Abstract: The present invention provides a method for determining all the molecular causes of Inherited Neuromuscular Disorders comprising determining a number of copy number variation(s), and/or determining a number of point mutation(s) on a physiological sample comprising a genome of a subject.

Abstract: The present invention relates to methods for restoring the function of a mutated dysferlin comprising the step of preventing splicing of one or more exons which encode amino acid sequences that cause said dysferlin dysfunction. Particularly, the splicing of exon 32 is prevented. The present invention also relates to a method for treating a dysferlinopathy in a patient in need thereof, comprising the step of administering to said patient antisense oligonucleotides complementary to nucleic acid sequences that are necessary for correct splicing of one or more exons which encode amino acid sequences that cause said dysfunction. Particularly, the splicing of exon 32 is prevented.

Abstract: The present invention relates to methods for restoring the function of a mutated dysferlin comprising the step of preventing splicing of one or more exons which encode amino acid sequences that cause said dysferlin dysfunction. Particularly, the splicing of exon 32 is prevented. The present invention also relates to a method for treating a dysferlinopathy in a patient in need thereof, comprising the step of administering to said patient antisense oligonucleotides complementary to nucleic acid sequences that are necessary for correct splicing of one or more exons which encode amino acid sequences that cause said dysfunction. Particularly, the splicing of exon 32 is prevented.

Abstract: The present invention relates to a composition comprising: a first adeno-associated viral (AAV) vector comprising: i) a 5?ITR (Inverted Terminal Repeat) sequence of AAV; ii) a portion of gene placed under the control of a promoter; iii) a sequence comprising a splice donor site; iv) a 3?ITR sequence of AAV; and/or a second adeno-associated viral (AAV) vector comprising; v) a 5?ITR (Inverted Terminal Repeat) sequence of AAV; vi) a sequence comprising a splice acceptor site; vii) a portion of gene; viii) a 3?ITR sequence of AAV. The combination of the portions of gene carried by the first and second AAV vectors comprises an open reading frame which encodes a functional dysferlin. In addition, the combination of the sequence comprising the splice donor site and the sequence comprising the splice acceptor site contains all the elements necessary for the splicing, advantageously derived from a natural intron of the dysferlin gene.