In a groundbreaking study, researchers evaluated the effectiveness of preventative therapies for spinal muscular atrophy (SMA) by comparing two well-matched groups of infants at risk of developing the disorder. This first-of-its-kind research, published in the Annals of Clinical and Translational Neurology by the Clinic for Special Children and Children’s Hospital of Philadelphia, focused on infants with either two or three copies of the SMN2 gene, which plays a crucial role in SMA. The study included 23 presymptomatic infants who received either gene therapy (onasemnogene abeparvovec) alone or in combination with oral risdiplam or intrathecal nusinersen, all administered before visible signs of the disease emerged.
Infants were divided into three groups: those with two SMN2 copies (SMA type 1) receiving only gene therapy, those with two SMN2 copies receiving dual therapy, and those with three copies (SMA type 2) receiving gene therapy only. The choice to incorporate a second therapy was made collaboratively by parents and healthcare providers as part of routine clinical management.
Researchers assessed therapy efficacy by measuring independent sitting and walking milestones and performing muscle ultrasounds and nerve conduction studies. The results indicated that while infants receiving dual therapy were able to sit independently sooner, they did not walk earlier than those on monotherapy. Additionally, muscle ultrasounds showed abnormal fat infiltration and fasciculations in both treatment groups, although infants with three SMN2 copies generally displayed normal muscle ultrasounds. Ultimately, while dual therapy was well tolerated, it did not prevent the progression of muscle disease. The researchers call for long-term studies to evaluate developmental outcomes for these infants.
