New paradigms in gene-based therapy for spinal muscular atrophy (SMA)

Spinal muscular atrophy (SMA) is a fatal genetic disease that affects thecontrol of muscle movement. It is caused by degeneration of lower motorneurons, in the spinal cord and the brainstem, leading to progressive paralysiswith muscular atrophy.Although some life-prolonging treatments for spinal muscular atrophy havebeen provided, these are not likely to be curative. A variety of innovativeapproaches have emerged. Among them, gene-based approaches to SMAtherapy are to correct the fundamental cause of the disorder by replacing themissing SMN1 gene. While preclinical studies of SMN gene-replacementtherapy in the SMNΔ7 animal model showed improvements in survival andmotor function with early treatment, the clinical findings fail to confirm thesedata, perhaps due to technical problems and safety concerns.Employing small RNA molecules to reprogram the splicing of a damaged premRNAis an expanding area of interest for a wide range of genetic disordersincluding SMA. While many of these strategies based on cell and gene therapyhold promise, the most intriguing results come from those which targetsplicing specifically anti-sense oligonucleotides that target negative elementsof exon 7 splicing in the SMN gene. This review assesses new paradigms ingene-based therapy for spinal muscular atrophies, their shortcomings andtherapeutic possibilities.

کلیدواژه ها:

Spinal muscular atrophy (SMA) ، Lower motor neuron disorder ، Gene therapy ، Molecular targets