Risdiplam Demonstrates Continued Improvements in SMA, Cortical Hyperexcitability in ALS, Retinal Atrophy Modulated With Rituximab

This week Neurology News Network covered the 2-year data from part 2 of the FIREFISH study of risdiplam in patients with spinal muscular atrophy, the prominence of cortical hyperexcitability in cognitively impaired patients with amyotrophic lateral sclerosis, and a study evaluating retinal atrophy in patients with multiple sclerosis treated with rituximab.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus.

Newly announced 2-year data from part 2 of the FIREFISH study of risdiplam (Evrysdi; PTC Therapeutics) in infants with type 1 spinal muscular atrophy demonstrated that the treatment continued to improve motor function between months 12 and 24, including the ability to sit without support. Results also showed that risdiplam continued to improve survival as well as the ability to feed orally, and reduced the need for permanent ventilation. These longer-term data build upon 1-year pivotal findings from FIREFISH part 2 that will be presented at the upcoming 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22. The primary end point, percentage of infants able to sit without support for at least 5 seconds at month 12, was met by 29% (12 of 41) of participants at 12 months and improved to 61% (25 of 41) by month 24. Furthermore, continued improvements in the ability to sit without support for at least 30 seconds were shown at month 24 indicated by 44% (18 of 41) of infants compared to 17% (7 of 41) at 12 months

Recently published data in Neurology revealed that cortical hyperexcitability was more prominent in cognitively impaired patients with amyotrophic lateral sclerosis (ALS), with associations between increases in short interval intracortical inhibition and cognitive dysfunction. These associations were independent of other transcranial magnetic stimulation (TMS) parameters, disease duration, or motor features. In total, 36% of the 40 patients with ALS in the cohort exhibited an abnormal total ECAS score. The prominence of cortical hyperexcitability in cognitively impaired patients with ALS was indicated by an increase in short interval intracortical facilitation. The study authors wrote, “Longitudinal studies assessing the evolution of cognitive and cortical excitability changes and relating these to structural and functional neuroimaging findings may provide greater understanding of the importance of cortical circuits in ALS pathogenesis, as well as provide information on the role of TMS parameters as outcome biomarkers in future therapeutic trials.”

Recently published results from an observational study revealed that retinal atrophy is modulated by rituximab (Rituxan; Genentech/Biogen) in patients with relapsing-remitting multiple sclerosis, with the greatest attenuation of retinal atrophy occurring after 12 months of treatment. Senior author Shiv Saidha, MD, professor of neurology, Johns Hopkins School of Medicine, and colleagues performed serial optical coherence tomography (OCT) scans on patients with RRMS treated with rituximab and compared rates of ganglion cell inner plexiform layer (GCIL) atrophy to patients treated with glatiramer acetate (GA) or natalizumab (Tysabri; Biogen), and healthy cohorts. Saidha and colleagues concluded, "our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, though should be confirmed by larger studies.”

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