Focus area: Physicians
The gene therapy arrives in Italy and rewrites the history of SMA
Experimentation of gene therapy on newborns with the most severe form of the disease also begins in Italy.
About one year after the arrival in Italy of the first drug in the world authorized for the treatment of spinal muscular atrophy (SMA), known as Nusinersen, another good news arrives for SMA families: within a few weeks, in Italy, the clinical study based on gene therapy, called AveXis 101, will be started and will be administered to newborns with genetically diagnosed and presymptomatic SMA. The news sounds like a liberating scream of hope, because it prefigures a scenario that until very recently seemed very unthinkable: cure a rare genetic disease like SMA, which prevents the body's voluntary muscles from walking, standing, sitting, swallowing . SMAs are a group of degenerative motor neuron diseases, characterized by degeneration of the anterior horn cells at the level of the spinal cord nucleus. All forms of SMA are associated with a mutation of the SMN1 gene, located on the long arm of chromosome 5 (5q12.3) that encodes the SMN (Survival of motoneurons) protein. In patients with type 1 SMA, lung diseases are the main causes of morbidity and mortality. If the Nusinersen, administered intrathecally, does not act on the mutated SMN1 gene, but modulating SMN2 splicing, allowing this second gene to produce a complete protein, the gene therapy is based instead on the intravenous administration of a correct copy of the defective gene (SMN1) encoding the missing SMN protein. The gene is carried within the organism through an adeno-associated virus serotype 9 (AAV9), non-pathogenic and, above all, able to cross the blood-brain barrier to reach the central nervous system. The first trial with AVXS-101, phase 1, was launched in 2014 at the Nationwide Children's Hospital in Columbus, Ohio, to first assess safety and, secondly, the effectiveness of 15 children, from 0 at 6 months, affected by SMA1. The results were published in November 2017, in the prestigious scientific journal New England Journal of Medicine: of the 12 patients who received the highest dose of gene therapy, 11 were able to sit without support, 9 were able to turn around themselves, and 2 were able to walk independently. The Gemelli Policlinico of Rome will be the first clinical center to start the trial in Italy. This is a phase 3 study, with a single intravenous administration of AVXS-101 that will be performed in children diagnosed with SMA, aged below 42 days of life at the date of dose administration, born after the thirty-fifth week of gestational age and who are not already on treatment with other drugs. After the Gemelli Policlinico five other clinical centers will be involved: the Southern NeMO of Messina, the G. Gaslini Institute of Genoa, the Besta Institute, the Policlinico of Milan and the Bambino Gesù Pediatric Hospital of Rome.