SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy

Abstract

Drugs that provide the splice of life Motor neurons relay signals from the nervous system to muscle fibers. In patients with spinal muscular atrophy, a protein required for the survival of these neurons is deficient or missing altogether, so the neurons gradually die and the patients' muscles waste away. The disease is currently untreatable. Naryshkin et al. discovered small-molecule drugs that cause cells to produce the missing protein by altering how a specific mRNA is put together, or “spliced” (see the Perspective by Vigevani and Valcárcel). When the researchers used the drugs to treat diseased mice, the mice showed marked improvement in muscle mass, motor function, and survival. Science , this issue p. 688 ; see also p. 624