Effect of COMT and UGT1A Variants on Clinical Response to Opicapone in Parkinson's Disease.

Variants in COMT and UGT1A modulate the response to opicapone (a catechol-O-methyltransferase inhibitor); low/medium/high COMT activity haplotypes.

Retrospective study of 237 Parkinson's disease patients treated with opicapone, genotyping COMT (rs4818, rs4680, rs4633, rs6269) and UGT1A (rs1105880). COMT rs4818 and rs6269 heterozygosity and the low-activity COMT haplotype were associated with improved motor fluctuations; the UGT1A rs1105880 dominant model was too. The medium-activity haplotype showed only a nominal association against dyskinesia worsening. No variant was associated with treatment discontinuation.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The work extends pharmacogenetics beyond the classic CPIC pairs toward a neurology gene-drug pair (COMT/UGT1A-opicapone). The rationale is coherent — COMT activity governs the very target of the inhibitor — but these are retrospective associations on composite endpoints, with no effect on discontinuation. Promising for personalised Parkinson's therapy, pending prospective confirmation before clinical use.

Analysis by Dr Thibaut Benquey