Spinal muscular atrophy is a rare neuromuscular disease caused by degeneration of the peripheral motor neurons, and leads to muscle loss. The most severe form of muscular atrophy usually causes the patient to die before the age of 2.
Proof of concept of a gene therapy strategy obtained and patented by Martine Barkats’ team at Genethon.
In 2019, a treatment based on these technologies gained marketing authorization in the US and then in France in 2020 for type 1 SMA and other types of SMA.
License agreement to Novartis
What is spinal muscular atrophy?
Spinal muscular atrophy is characterized by degeneration of the nerve cells that control muscle movement, the peripheral motor neurons, specifically the part referred to as the anterior horn, of the spinal cord and the lower part of the brain (brainstem). The muscle fibers cannot survive without the neurons that innervate them. The decrease in the number of muscle fibers causes weakness and muscle loss (atrophy).
There are several forms of spinal muscular atrophy of genetic origin. The most common form is the one related to abnormalities detected in the SMN1 (SMA) gene, located on chromosome 5. There are several types – from I to IV – depending on the age of onset of the disease and the extent of the loss of muscle strength.
Type I, the acute form of SMA, is the most severe. It manifests at birth or before 6 months of age, causing severe hypotonia and motor dysfunction of all four limbs and trunk. The patient usually dies in the first two years of life due to respiratory failure. These conditions affect one in 6,000 newborns, and in France we estimate that between 80 and 100 children with SMA are born each year.
Spinal muscular atrophy: Genethon’s role
Genethon has been working to develop a gene therapy for type I SMA since 2004.
Proof of principle of the efficacy of a gene therapy strategy via administration of an AAV (Adeno Associated Virus) vector carrying the human Smn1 gene sequence was obtained in a mouse model of SMA by Dr. Martine Barkats’ team (Dominguez et al., Hum Mol Genet 2010). Its pioneering work to design a therapeutic vector also demonstrated that the use of a specific AAV vector could treat patients’ motor neurons via injection into the bloodstream.
Spinal muscular atrophy: what’s happening today?
In 2019, a gene therapy treatment using technologies from Genethon obtained marketing approval in the United States, then in France in 2020 for type I SMA and other types of SMA (find out more about these approvals in the United States and in Europe). In France, the cost of this treatment is covered by standard public health insurance.
Spinal muscular atrophy: testimonials