Michael Hayden, MB, ChB, PhD, FRCP, FRSC, The University of British Columbia, Vancouver, Canada, comments on the potential of sigma-1 receptor (S1R) agonism as a therapeutic strategy for numerous neurological disorders. Pridopidine is a potent, highly selective, oral S1R agonist currently under investigation in the Phase III PROOF-HD study for the treatment of Huntington’s disease (HD). However, its mechanism of action is likely to have value beyond this setting. For example, mutations in the S1R gene leading to loss of function of the protein can cause amyotrophic lateral sclerosis (ALS). Pridopidine is therefore being assessed in the Healey ALS Platform Trial (NCT04297683) for the treatment of ALS. By acting to reduce cellular stress and neuroinflammation, enhance toxic protein clearance, and increase neuroprotection, S1R agonism has also shown benefits in preclinical models of Parkinson’s disease, Alzheimer’s disease, and several neurodevelopmental disorders. This interview took place during the European Huntington’s Disease Network 2022 Plenary Meeting.
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