Longitudinal data of the European prospective natural history study of patients with type 2 and 3 spinal muscular atrophy

Spinal muscular atrophy (SMA) is the second most frequent autosomal recessive disorder worldwide affecting approximately 1 in 10,000 people. Clinical manifestations include muscle atrophy and varying degrees of weakness. Several therapeutic strategies for treatment of SMA are under investigation including SMN2 splicing modifiers and gene therapy. Recently, Trophos reported positive results in a phase III trial for olesoxime in non-ambulant type 2 and 3 SMA. However no effective treatment has currently received market approval. Due to the variability in SMA phenotypes, it is important to determine the best outcome measures to assess the efficacy of potential therapies and the prognostic factors for the disease. We present here a prospective natural history study of type 2 and 3 SMA patients to characterize the disease course by using standardized evaluations. A total of 70 patients aged 2 to 30 years are planned to be enrolled in Belgium, France and Germany. Visit frequency and assessments are adjusted to age, ambulatory and respiratory status. Evaluations include clinical exam, pulmonary function tests, electrophysiology and NMR measurements, strength and motor function assessments using upper limb-specific devices (MyoSet and Active-Seated), MFM scale and standard timed tests, activity monitoring using the Actimyo device and quality of life assessment. Blood samples are collected to determine the copy number of SMN2 gene, and to analyze SMN mRNA, SMN protein and exploratory biomarkers. Data from the patients' usual follow-up care are collected from their medical files including psychomotor development, respiratory function, feeding and orthopedic status. According to the fatigability of the patient, the assessments can be performed on one or two days. These data will help to characterize the disease course and spectrum of SMA and may help to empower future therapeutic studies as well as to eventually reduce the need for placebo groups.