A Johns Hopkins Children’s Center-led study shows that patients with spinal muscular atrophy (SMA) could regain muscle with the help of a new monoclonal antibody treatment. Researchers say the study findings, published Aug. 13 in Lancet Neurology, demonstrate improved motor function in children with SMA who are unable to walk.

Affecting 1 in 15,000 individuals, spinal muscular atrophy is one of the most common genetic neuromuscular disorders, and affects individuals of all ages, though most are weak from infancy or early childhood. Experts say in the past decade three new therapies — nusinersen, risdiplam and gene therapy onasemnogene abeparvovec — have greatly altered the inevitably declining clinical course. SMA is no longer a leading cause of death in infancy. But while these therapies effectively target the motor neuron degeneration of SMA, many who receive them remain weakened with important limitations of motor function.

Now, a new therapy builds upon findings from Johns Hopkins researchers led by Se-Jin Led in 1997 that discovered myostatin, a hormone that regulates muscle mass. Following a proof-of-concept trial of apitegromab, a monoclonal antibody that alters levels of myostatin, Thomas Crawford, M.D., professor of neurology at the Johns Hopkins University School of Medicine, says this is the first demonstrated therapy, after more than a decade of intensive commercial research, to find a way to use this natural hormone for therapeutic benefit.

Crawford, who is also a pediatric neurologist at the Children’s Center, and a team of researchers investigated whether apitegromab could safely improve muscle function in a large study of patients with SMA. From April 14, 2022, to Sept. 4, 2024, 188 patients between 2 and 21 years old with nonambulatory type 2 or type 3 SMA who were receiving nusinersen or risdiplam at 48 hospitals in nine countries in Europe and North America were enrolled for the latest trial. Participants were randomized to receive apitegromab or a placebo intravenously every four weeks.

At 12 months, the research team says participants receiving apitegromab showed statistically significant and potentially clinically meaningful improvements in motor function compared with participants receiving the placebo. Both groups were evaluated on the Hammersmith Functional Motor Scale-Expanded (HFMSE), a special tool developed to evaluate physical abilities in people with SMA types 2 and 3.

“Based on our findings, apitegromab has the potential to positively impact people with SMA, particularly those with weakened muscles who are unable to walk, allowing them to build muscle again and improve quality of life,” Crawford says.

Crawford and the research team plan next to study whether or not apitegromab will provide benefit to a broader group of patients with muscle weakness due to muscular dystrophy or other neuromuscular conditions.