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Framework analysis demonstrates pharmacogenetic stratification strategies in Parkinson's disease, highlighting the need for sensitive endpoints to detect genotype-treatment interactions.
The biological heterogeneity of Parkinson’s disease impedes disease-modifying trials and demands stratified approaches. We present a framework applying pharmacogenetics across three domains: mechanistic stratification, drug-host interactions, and prognostic enrichment. Genetic heterogeneity operates from polygenic scores to single variants, and mechanistic and prognostic effects may conflict with direct consequences for trial power. Realising this potential requires larger stratified trials, sensitive endpoints and collaborative infrastructure to detect genotype-by-treatment interactions with adequate power.
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Gurney et al. (2026) studied this question.
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