Lancet neurology
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Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated neurological deficits. Although drug-resistant epilepsy is not synonymous with unresponsiveness to any drug treatment, the probability of achieving seizure freedom on a newly tried medication decreases with increasing number of previously failed treatments. ⋯ Substantial evidence indicates that a delay in identifying an effective treatment can adversely affect ultimate outcome and carry an increased risk of cognitive disability, other comorbidities, and premature mortality. Research on mechanisms of drug resistance and novel therapeutics is progressing rapidly, and potentially improved treatments, including those targeting disease modification, are on the horizon.
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of venglustat in GBA1-associated Parkinson's disease: an international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.
Variants in the GBA1 gene, which encodes lysosomal acid glucocerebrosidase, are among the most common genetic risk factors for Parkinson's disease and are associated with faster disease progression. The mechanisms involved are unresolved but might include accumulation of glucosylceramide. Venglustat is a brain-penetrant glucosylceramide synthase inhibitor that, in previous studies, reduced amounts of the glycosphingolipid. We aimed to assess the safety, efficacy, and target engagement of venglustat in people with early-stage Parkinson's disease carrying pathogenic GBA1 variants. ⋯ Sanofi.