Although Gene Therapy Offers Hope, SMA Patients Still Face Significant Health Challenges

Children with spinal muscular atrophy (SMA) experience benefits from receiving a disease-modifying gene therapy, but many still end up developing serious complications, including spinal deformities, respiratory issues, and in some cases, death, according to a recent study.

The study, led by Isabelle Desguerre, M.D., of Paris University, followed 29 children who received Zolgensma (onasemnogene abeparvovec), a gene replacement therapy, over a two-year period, revealing a mixed picture of progress and ongoing challenges. The research found 90% of the patients were able to sit unassisted after two years, and 70% could stand with assistance. Motor scores also significantly improved for all patients.

Despite these gains, nearly 90% of the children followed in the study still developed spinal deformities and required braces. Some also needed feeding assistance or noninvasive ventilation. Researchers also documented two deaths shortly after treatment, one due to respiratory failure and another caused by a severe complication known as thrombotic microangiopathy.

SMA is a rare genetic disorder that leads to severe muscle weakness, often appearing within the first six months of life. Without treatment, most children with the condition die before the age of 2 from respiratory failure. The approval of three disease-modifying medications since 2016 have transformed the treatment landscape. In addition to Zolgensma, the other available medicines are Spinraza (nusinersen) and Evrysdi (risdiplam), which don’t cure the SMA but modify the underlying disease process. Now, with early screening and presymptomatic treatment shortly after birth, babies with SMA can achieve normal motor milestones.

Children with a more severe form of the disease may not benefit from the available gene therapies, even at a young age. The study, published in Orphanet Journal of Rare Diseases, identified 95 children diagnosed with SMA between June 2019 and June 2022 in France. Among those patients, 41 were excluded due to poor prognosis with initial severe bulbar signs and respiratory distress and were directed toward palliative care.

While Zolgensma was generally well-tolerated, side effects included elevated liver enzymes and respiratory infections. The children in the study were treated approximately between 2 months and 1 year of age. The researchers stressed the importance of ongoing monitoring and care for SMA patients, even as gene therapy improves their ability to meet developmental milestones.