Aromatic L-Amino Acid Decarboxylase Gene Therapy Enhances Levodopa Response in Parkinson's Disease.

Movement Disorders : Official Journal of the Movement Disorder Society
John G NuttChadwick W Christine

Abstract

As Parkinson's disease progresses, levodopa treatment loses efficacy, partly through the loss of the endogenous dopamine-synthesizing enzyme L-amino acid decarboxylase (AADC). In the phase I PD-1101 study, putaminal administration of VY-AADC01, an investigational adeno-associated virus serotype-2 vector for delivery of the AADC gene in patients with advanced Parkinson's disease, was well tolerated, improved motor function, and reduced antiparkinsonian medication requirements. This substudy aimed to determine whether the timing and magnitude of motor response to intravenous levodopa changed in PD-1101 patients after VY-AADC01 administration. Participants received 2-hour threshold (0.6 mg/kg/h) and suprathreshold (1.2 mg/kg/h) levodopa infusions on each of 2 days, both before and approximately 6 months after VY-AADC01. Infusion order was randomized and double blinded. Unified Parkinson's Disease Rating Scale motor scores, finger-tapping speeds, and dyskinesia rating scores were assessed every 30 minutes for 1 hour before and ≥3 hours after start of levodopa infusion. Of 15 PD-1101 patients, 13 participated in the substudy. Unified Parkinson's Disease Rating Scale motor score area under the curve responses to threshold and suprath...Continue Reading

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Citations

Apr 3, 2020·Nature Reviews. Neurology·Heather Wood
Aug 21, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren OlanowJose A Obeso
Jul 3, 2021·International Journal of Molecular Sciences·Ana Fajardo-SerranoJosé Luis Lanciego
Aug 10, 2021·Journal of Parkinson's Disease·Tomas Björklund, Marcus Davidsson

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