In the study entitled “Observational study of spinal muscular atrophy type I and implications for clinical trials” published in the Neurology journal, the authors describe the clinical features of spinal muscular atrophy type I, data that can be useful to future design of clinical trials.
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a genetic mutation in the Smn1 gene (short for spinal motor neuron-1). The lack of SMN1 protein leads to the death of motor neurons and consequently, muscle atrophy. The disease is the leading cause of child death among genetic disorders and currently has no cure. SMA is divided, according to motor function, into four different phenotypes – type I (SMA-I, onset by 6 months), type II (SMA-II, onset 6–18 months), ambulatory type III children, and type IV adults.
In this study, patients with SMA-I were followed at 3 study sites for up to 36 months with registration of clinical features, including serial clinical, motor function, laboratory, and electrophysiologic outcomes. From the 54 eligible patients with SMA-I, 34 patients were enrolled in the study with 50% of them being followed for at least 12 months. The authors found that the median age patients reached the primary endpoint, death, or the necessity for 16 hours of ventilation support per day was 13.5 months. Nutrition support was required previously to ventilation. Patients with symptoms within 3 months of age and after this period, showed no differences on the period reaching the primary endpoint. For SMA-II, gene copy was associated with disease severity, specifically, two copies of Smn2 triggered a higher rate of morbidity and death when compared to 3 copies.
The authors suggest that patients with SMA-I can enroll in longitudinal studies, but this should occur within 8 months after diagnosis, since after this period, a higher risk for feeding support was observed. The patients were available for extensive testing with appropriate resting periods. Additionally, the authors highlight that SMN2 copy number is a predictive biomarker for patients’ stratification. These findings are key, since drug developers have reported significant difficulty in conducting clinical trials with type I SMA. New best practices that would allow for improved participation in clinical trials for SMA Type I therapies.