Summary

Spinal muscular atrophy, the leading inherited killer of children, has forced generations of parents to watch their kids become progressively weaker and, in severe cases, die by about their second birthdays. The recessively inherited disease inexorably destroys the motor neurons of the spinal cord and brain stem, hobbling muscle movement, including breathing. But now, building on a deep understanding of the biology of the disease, biologists have produced a breakthrough drug that is on the brink of regulatory approval. Nusinersen is an antisense therapy that restores cells' ability to make a protein that is vital to the survival of motor neurons and that is largely absent in children with the disease, who carry a mutated form of the key gene that produces this protein. Two recent, late-stage clinical trials were stopped because nusinersen, developed by Ionis of Carlsbad, California, and now licensed to Biogen of Cambridge, Massachusetts, was so effective in restoring motor function in children and babies that it was deemed unethical to deny the drug to children in the placebo arms of the trials. Neuroscientists are optimistic that the success of nusinersen may portend similar positive results for antisense therapies now being developed to fight other genetically linked nervous system diseases like amyotrophic lateral sclerosis and Huntington disease.