Gene Therapy can Reverse Effects of Spinal Muscular Atrophy in Mice

adeno-associated virus
Adeno-associated viruses are attractive for gene therapy because of their apparent lack of pathogenicity. Image: Wikipedia - Graham Colm
Spinal muscular atrophy (SMA), a muscle-wasting disease caused by a deficiency in survival motor neuron protein (SMN), is a leading genetic cause of death in infants. There is currently no cure for the disease and treatment consists of managing the symptoms and preventing complications. The protein deficiency, which is restricted to motor neurones, is caused by loss of or mutation in the SMN 1 gene and a team led by researchers at Ohio State University have shown that, in mice at least, the disease can be reversed by intravenous, virally mediated gene delivery.

SMA mice, treated at one day old, showed increased levels of SMN in the brain, spinal cord and muscles within ten days. Although levels remained lower than in normal mice, the increase appeared to be sufficient to reverse the effects of the disease and the team believe that the same would be true in children with the disease. Dramatic improvements were seen only in mice treated within the first two days of life and the potential treatment window for children is not yet clear. The researchers hope to be able to progress to human clinical trials and, as a first step, have shown that the virus is also able to cross the blood-brain barrier and penetrate motor neurones in a one day old macaque. One difficulty in translating the research into a treatment option for children with SMA is that symptoms are typically absent in very young infants and the only available screening method for newborns is considered to be prohibitively expensive.

The study is published in Nature Biotechnology.