Physical Therapy Boosts Efficacy of Nusinersen in SMA, Study Shows

The inclusion of physical therapy alongside Spinraza (nusinersen) leads to significantly better motor skill improvements in people with spinal muscular atrophy (SMA) vs nusinersen alone, according to a new study.

The findings suggest that frequent physical therapy is an essential component of SMA treatment, according to the investigators. People with SMA have an insufficient level of survival motor neuron (SMN) protein, the results being muscle waste and motor deficiencies. The genetic disease is a leading cause of infant mortality, they added.

Nusinersen was the first of 3 therapies approved by the FDA to treat SMA. It targets SMN2 pre-mRNA. SMN2 is one of 2 genes that encode the SMN protein.

Writing in Frontiers in Bioscience - Landmark Edition, the authors explained that nusinersen helps create functional SMN proteins, leading to improvements in motor function, respiratory status, and nutritional status.

The investigators said physical therapy is an important part of the standard of care, as it can help maintain range of motion, increase muscle strength, and improve mobility. In the new report, the authors sought to better understand the role physical therapy plays in improving outcomes in patients taking nusinersen.

They recruited 55 children and adolescents with SMA who were taking nusinersen. The cohort included patients with SMA types 1, 2, and 3, and patients were split up based on their access to weekly physical therapy. Most participants (39) were in the nusinersen-plus-physical-therapy group. The remaining 16 patients received nusinersen alone or with infrequent physical therapy.

Over the course of the study, patients’ motor evolution was evaluated by licensed physical therapists with SMA experience using SMA-specific assessments. Those evaluations took place at baseline (before nusinersen initiation), after 6 months on nusinersen, and after 1 year on the therapy.

Overall, the patients in the physical therapy group experienced a 12.66% improvement in their motor skill performance at 12 months compared with a 3.18% improvement in the nusinersen-alone group. The authors noted there was variability in the results between patients with different types of SMA. Patients with SMA type 1 had greater improvements than those with type 2. Type 1 is infantile-onset SMA and is the most common type. These patients typically do not live beyond 2 years. People with type 2 SMA generally experience disease onset after 6 months of age and have longer life expectancy.

The investigators said it is not clear why people with type 1 SMA appeared to benefit more.

“At this moment, we assume it is due to motor neuron loss and chronic denervation in patients with type 2 that started treatment long after they were diagnosed (as a consequence of the lack of treatment until 2018 - in Romania),” the authors wrote. They said other factors could also be responsible.

The investigators said starting treatment as quickly as possible is essential in order to preserve as many motor neurons as possible. “However, the administration of nusinersen alone is not expected to provide the best outcome in symptomatic SMA patients,” they concluded. “In addition to therapy, it is critical that the standards of care be followed completely and correctly.”

Those standards should include regular physical therapy at least 5 times per week, the authors said.

Reference
Mirea A, Leanca MC, Onose G, et al. Physical therapy and nusinersen impact on spinal muscular atrophy rehabilitative outcome. Front Biosci (Landmark Ed). 2022;27(6):179. doi:10.31083/j.fbl2706179