Muscular dystrophies are clinically heterogeneous diseases, characterized by the primary wasting of skeletal muscle that compromises patient’s mobility and their respiratory and cardiac functions, thus leading to wheelchair dependency, respiratory failure and premature death. Duchenne muscular dystrophy (DMD) is the most common and severe.
DMD, which still meets no cure, affects one male newborn in 3,500 as it is a recessive X-linked disorder, characterized by a mutation in dystrophin gene. Dystrophin deficiency, at sarcolemma level, decreases fibres elasticity and leads to a loss in muscle force which is associated with skeletal myofibers degeneration. In DMD patients, the first symptoms appear around the age of 3-5. Progressive loss in muscle force is linked to a reduced motility and wheelchair dependency which arises at the age of 10-14 in 97% cases. In most cases, death occurs before 30s for respiratory and cardiac complications.
Currently many novel approaches, from medicinal treatment to a combination of gene and cell therapies, have been tested. The latter strategy, as in the case of exon skipping technique, might be one of the most promising as it is apt to induce muscle regeneration by autologous stem cell transplantation. Stem cells are isolated from the same patient and genetically corrected through a lentiviral vector, which is able to skip the mutation exons in dystrophin gene in order to restore its reading frame and give rise to a shorter but functional dystrophin protein. The exon skipping method confers the advantage to be directed against the mutated endogenous dystrophin transcripts, preserving the natural level of the protein. Moreover, autologous transplantation allows circumventing the problem of immune response encountered either during gene therapy approaches using direct in vivo viral vector administrations or during allotransplantation. Based on these findings, several clinical trials in patients have been planned and some of them are now being funded. However, factors like safety and sustained beneficial effects in patients will have to be considered in detail before this technology can be widely extend for the treatment of muscular disorders.