Th

Tyrosine hydroxylase (TH), also termed dopamine synthesis enzyme, serves as the rate-limiting catalyst in catecholamine biosynthesis. This mitochondrial enzyme converts tyrosine to L-DOPA, the precursor for dopamine, norepinephrine, and epinephrine production. TH deficiency underlies Segawa syndrome, a rare genetic disorder causing progressive dystonia and motor dysfunction, while its marked reduction in substantia nigra neurons drives dopamine depletion in Parkinson’s disease.
Current therapies focus on L-DOPA supplementation, though prolonged use triggers dyskinesias. Oxford Biomedica’s OXB-102 employs adeno-associated virus (AAV) vectors to deliver TH genes, demonstrating sustained dopamine restoration in primate models. Merck’s MK-8318, a novel allosteric activator, enhances TH activity without bypassing feedback regulation, currently in Phase I trials. Challenges remain in achieving targeted brain delivery and mitigating compensatory neurotransmitter imbalances, necessitating advanced formulation strategies for clinical translation.