A new clinical trial has revealed encouraging results for a muscle-targeting therapy aimed at improving motor function in children and adolescents with spinal muscular atrophy, according to a study published in The Lancet Neurology.
Spinal muscular atrophy (SMA) is a rare genetic disorder that affects motor neurons — nerve cells in the spinal cord responsible for controlling voluntary muscle movement. Caused by mutations in the SMN1 gene, SMA leads to progressive muscle wasting and weakness, and can severely impact mobility, breathing and swallowing.
SMA is one of the most common genetic conditions affecting children, with an estimated 1 in every 6,000 to 10,000 babies born worldwide with the condition.
While current treatments help slow disease progression and improve motor milestones, they do not fully restore muscle strength or function. Even mild improvements in motor function, however, can significantly improve a child's quality of life, said co-author Nancy Kuntz, MD , Medical Director, Mazza Foundation Neuromuscular Program at Ann & Robert H. Lurie Children's Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine.
"Gene replacement therapy has been very effective for SMA. But this and other motor neuron targeted therapies are not cures. There's been a real flurry of activity trying to figure out ways of getting the treatment started earlier so that there are fewer motor neurons lost. Inclusion of SMA in the Newborn Screening in the US has been a great improvement," Kuntz said. "However, SMA patients, particularly those beginning treatment when symptomatic, have weakness as compared to peers and over time can experience some loss of function."
The current trial, conducted across 48 hospitals in Europe and the U.S., evaluated the safety and efficacy of the new drug in 188 patients aged 2 to 21 years with non-ambulatory type 2 or type 3 SMA. All participants were already receiving standard-of-care treatments prior to the trial.
The drug, apitegromab, is designed to inhibit myostatin activation, a biological process that limits muscle growth. By targeting this pathway, investigators hoped to enhance muscle strength and function in SMA patients, who typically experience progressive muscle weakness.
Among children aged 2 to 12, those treated with the drug showed a statistically significant improvement in motor scores, compared to those receiving a placebo.
"All of these individuals could sit or walk, but they did not have normal mobility," Kuntz said. "While improvements seen on the drug were not something that would be the difference between being bedridden and walking, the changes led to functional independence. Being able to facilitate some kind of movement so patients can interact with their environment is incredibly meaningful and allows them to be a little bit more independent, have more dignity and improve their quality of life."
Although the results were encouraging, more work is needed to ensure patients have access to therapies that delay progression of the disease, Kuntz said.
"The therapy is a bit of a challenge for individuals to undergo long-term because it requires intravenous administration once every month," Kuntz said. "There are other types of myostatin inhibition that have been developed with subcutaneous injection, which is under the control of the individual themselves at home. Apitegromab is being developed for subcutaneous administration, but it will take several years to get that to be commercially available."
Moving forward, Kuntz and her collaborators will continue to study new treatments for SMA, with the goal of halting motor function loss in children, she said.
The study was funded by Scholar Rock, the biotechnology company developing apitegromab.
Ann & Robert H. Lurie Children's Hospital of Chicago is a nonprofit organization committed to providing access to exceptional care for every child. It is the only independent, research-driven children's hospital in Illinois and one of less than 35 nationally. This is where the top doctors go to train, practice pediatric medicine, teach, advocate, research and stay up to date on the latest treatments. Exclusively focused on children, all Lurie Children's resources are devoted to serving their needs. Research at Lurie Children's is conducted through Stanley Manne Children's Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is the pediatric training ground for Northwestern University Feinberg School of Medicine. It is ranked as one of the nation's top children's hospitals by U.S. News & World Report.
