Natural History of Type 2 and 3 Spinal Muscular Atrophy (SMA): Longitudinal 2-year NatHis-SMA Study (530)

Objective: NatHis-SMA (NCT02391831) is a prospective study of the natural history of patients with Type 2 and 3 spinal muscular atrophy (SMA). The objectives of this study were to: characterize the disease course of untreated patients; identify prognostic variables of disease and biomarkers of SMA; and identify the best outcome measure for further therapeutic approaches.

Background: SMA is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. Defining the natural history of SMA is essential for identifying reliable outcome measures for different patient populations. Current outcome measures may require 3-year follow up to identify significant change.

Design/Methods: NatHis-SMA was conducted in nine centers across Europe between May 2015 and May 2018. Individuals with genetically confirmed SMA (Type 2 or 3), aged 2–30 years, were eligible. Participants were assessed on several measures, including motor function (e.g. MFM20/MFM32) and movement monitoring (magneto inertial technology, ActiMyo®), upper limb strength and function (Myopinch®/Myogrip® and MoviPlate), intramuscular fat changes (MRI), pulmonary function and quality of life. Measures were performed every 6 and/or 12 months for 24 months.

Results: Baseline assessments were completed by 81 patients and 40 patients were assessed at 24 months. MFM32 significantly decreased over 2 years in all SMA types. Upper limb strength also decreased over a 1 and 2-year period. Upper limb activity and power as measured by ActiMyo® significantly decreased over a 6 month and a 1-year period.

Conclusions: These assessments represent highly relevant, clinically meaningful outcome measures for individuals with SMA and are highly sensitive to change; they allow trials to be conducted with significantly fewer patients or during shorter periods of time. Application of these measures to future clinical trials could provide a holistic evaluation of disease progression and treatment efficacy.

Disclosure: Dr. Servais has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis, Inc., Biogen, Biophytis, Cytokinetics, Dynacure, Roche, Santhera, Sarepta Therapeutics. Dr. Servais has received research support from Avexis, Inc., Biogen, Dynacure, and Roche. Dr. Seferian has nothing to disclose. Dr. Daron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis. Dr. Pereon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis, Roche, PTC, Akcea, Alnylam. Dr. Cances has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AVEXIS and BIOGEN. Dr. Vuillerot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC therapeutics; Biogen; Avexis; Roche. Dr. Vuillerot has received research support from Roche. Dr. De Waele has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis and Biogen. Dr. Laugel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Biogen, Avexis, Sarepta. Dr. Schara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Avexis, PTC, Sarepta, Genzyme. Dr. Schara has received personal compensation in an editorial capacity for Nikup. Dr. Gidaro has nothing to disclose. Dr. Lilien has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Biogen. Dr. Lilien has received compensation for serving on the Board of Directors of Roche, Biogen. Dr. Hogrel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Sarepta. Dr. Baudin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultants for Research in Imaging and Spectroscopy (CRIS). Dr. Carlier has nothing to disclose. Dr. Fournier has nothing to disclose. Dr. Lowes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ATOM International. Dr. Lowes has received royalty, license fees, or contractual rights payments from Nationwide Children’s Hospital. Dr. Gorni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F.Hoffmann-La Roche. Dr. Moal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman La Roche.. Dr. Hellbach has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Seabrook has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Czech has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Therachon AG, Basel. Dr. Czech has received compensation for serving on the Board of Directors of Therachon AG, Basel. Dr. Czech holds stock and/or stock options in Therachon AG, Basel Switzerland, VectivBio AG, Basel Switzerland, Roche, Basel Switzerland, Pfizer, NY, USA. Dr. Hermosilla has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Annoussamy on behalf of the Na has nothing to disclose.