Methods and means for efficient skipping of at least one of the following exons of the human duchenne muscular dystrophy gene: 43, 46, 50-53

Abstract

The invention relates a method wherein a molecule is used for inducing and / or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and / or said patient with a molecule. The invention also relates to said molecule as such.

Description

[0001]This U.S. patent application is a continuation of PCT / NL2009 / 050113, filed on Mar. 11, 2009 which claims priority to PCT / NL2008 / 050673, filed on Oct. 27, 2008, which claims priority to European application no. 07119351.0, filed on Oct. 26, 2007, which claims the benefit of U.S. provisional patent application No. 61 / 000,670, filed on Oct. 26, 2007, the entirety of which is incorporated herein by reference. The invention relates to the field of genetics, more specifically human genetics. The invention in particular relates to modulation of splicing of the human Duchenne Muscular Dystrophy pre-mRNA.BACKGROUND OF THE INVENTIONField[0002]Myopathies are disorders that result in functional impairment of muscles. Muscular dystrophy (MD) refers to genetic diseases that are characterized by progressive weakness and degeneration of skeletal muscles. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most common childhood forms of muscular dystrophy. They are re...

AI Technical Summary

Benefits of technology

[0022]Alternatively, a method of the invention may improve one or more characteristics of a muscle cell of a patient or alleviate one or more symptoms of a DMD patient having small mutations in, or single exon duplications of exon 43, 46, 50-53 in the DMD gene, occurring in a total of 36% of all DMD patients with a deletion (Aartsma-Rus et al, Hum. Mut. 2009)

[0026]An alleviation of one or more characteristics may be assessed by any of the following assays on a myogenic cell or muscle cell from a patient: reduced calcium uptake by muscle cells, decreased collagen synthesis, altered morphology, altered lipid biosynthesis, decreased oxidative stress, and / or improved muscle fiber function, integrity, and / or survival. These parameters are usually assessed using immunofluorescence and / or histochemical analyses of cross sections of muscle biopsies.

Problems solved by technology

Myopathies are disorders that result in functional impairment of muscles.

DMD mutations in the DMD gene are characterized by frame shifting insertions or deletions or nonsense point mutations, resulting in the absence of functional dystrophin.

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