Spinal muscular atrophy (SMA) is a genetic disease that can leave infants with weak muscles and trouble breathing. Many with the disease die before age two. To help these patients, doctors need therapies that target the genetic mutation and stop its progression.
Now, scientists at the California Institute for Biomedical Research (Calibr) and The Scripps Research Institute have discovered how a potential new drug targets SMA. The research, published recently in the journal Proceedings of the National Academy of Sciences, could guide the development of other drugs for genetic diseases.
“In fact, if we can learn more about the drugs in the pipeline for genetic diseases, we can learn more about the diseases themselves,” says Kristen Johnson, PhD, a principal investigator at Calibr and co-lead author of the study.
Until recently, patients diagnosed with SMA had no treatment options. The recent approval of a drug called nusinersen, marketed as Spinraza, has given families hope, and now scientists are working to design therapies that could be even more effective.
One potential drug is RG-7916, a small molecule currently in phase 2 clinical trials run by pharmaceutical company Roche (which no had involvement in this study). In the study, Johnson and her colleagues examined molecules similar to RG-7916 to better understand how the drug works.
“Understanding the mechanisms behind drugs is so critical for treating the right kinds of patients,” Johnson says. “Plus, the more you understand about the mechanism of a drug, the better physicians can watch out for possible side effects.”
The researchers suspected that to really be effective, RG-7916 would need to target a process called RNA mis-splicing. In addition to causing SMA, RNA mis-splicing is responsible for a family of devastating genetic illnesses, from Hutchinson-Gilford progeria syndrome, which causes premature aging, to Menkes disease, which causes severe neurological impairment and often kills patients before age three.