A novel gene therapy approach for the treatment of amyotrophic lateral sclerosis (ALS) has been trialled successfully in mice by researchers at Sorbonne Universités. The approach targeted the suppression of the toxic mutant SOD1 in the affected tissues.
Adeno-associated virus serotype rh10 vectors (AAV10) were used to mediate exon skipping of the hSOD1 pre-mRNA by expression of exon-2-targeted antisense sequences embedded in a modified U7 small-nuclear RNA (AAV10-U7-hSOD). A premature termination codon was generated by skipping the hSOD1 exon, the deleted transcript that was subsequently produced was degraded by the activation of nonsense-mediated decay. AAV10-U7-hSOD was administered to the mice in the trial with a combination of both intravenous and intracerebroventricular delivery.
The results, published in Molecular therapy reported that mice injected either at birth or at 50 days of age had significantly increased survival rates (by 92% and 58%, respectively). The therapeutic effects also extended to the prevention of weight loss and decline in neuromuscular function.
The team believes that their exon-skipping approach supports ‘the translation of this technology to the treatment of this as yet incurable disease.’
Source:A New AAV10-U7-Mediated Gene Therapy Prolongs Survival and Restores Function in an ALS Mouse Model. Biferi M G et al., Molecular therapy June 2017. DOI