Risdiplam: therapeutic effects and tolerability in a small cohort of 6 adult type 2 and type 3 SMA patients

Abstract Background Risdiplam is a validated treatment for adult SMA patients, but clear guidelines concerning functional assessment at baseline and during the follow-up are still limited, especially in terms of sensible and validated outcome measures able to capture minimal changes in motor performances induced by therapy. The aim of this work is to describe the effect of Risdiplam on a cohort of 6 adult type 2 and type 3 SMA patients, using Motor Function Measure (MFM32) as a standardized scaleto quantify the motor improvements induced by therapy. Results Risdiplam at the dose of 5 mg/daily was administered to a population of 6 (4 F;2 M) type 2 (N = 4) and type 3 (N = 2), adult SMA patients. Two patients were previously treated by Nusinersen, later suspended due to side effects. At baseline, all patients received a neuromuscular evaluation and a MFM32 assessment. After the beginning of treatment, we evaluated MFM32, patient reported outcomes (PROs), and adverse events over 7–27 months of follow-up. The MFM32 showed an increased score ranging from + 2.16% to + 7.29% in 4 patients. The improvement was maintained overtime, with two patients presenting the longest follow-up period of 24 and 27 months respectively. Subdomain D3 was ameliorated in 66.6% of patients. Two patients previously treated with Nusinersen maintained the pre-Risdiplam scores. The HFMSE was also performed and failed to show significant improvements after treatment. All patients reported subjective ameliorations. The commonest PROs were improvements in breath fatigue, voice’s intelligibility, hand strength and dexterity. Adverse effects were mild and decreased over time. Conclusions Risdiplam is a well-tolerated treatment in our cohort of adult type 2 and type 3 SMA patients and resulted in improvement or stabilization in motor functions. MFM32 proved to be sensitive to detect changes induced by therapy. Subjective meaningful improvements were sustained overtime especially in bulbar functions, breath fatigue and distal motor abilities.