AADC gene therapy brings hope to Parkinson's disease patients

This article comes from the NEJM Journal Watch Three-Year Outcomes of Gene Therapy for Parkinson Disease after receiving gene therapy.
Commentary author: Michael S.
Okun, MD gene therapy (including levodopa The gene encoding the enzyme that converts to dopamine) has shown good prospects in the phase 1b study
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Aromatic L-amino acid decarboxylase (AADC) is an enzyme that converts levodopa into dopamine
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As Parkinson's disease progresses, the substantia nigra striatum cells that produce AADC decrease, so patients need to increase the dose of levodopa or add other treatments to control movement fluctuations and dyskinesias
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The researchers published the 36-month safety and clinical outcome of NBIb-1817 (VY-AADC01, an investigational gene therapy for the treatment of Parkinson's disease [not yet FDA approved]) Phase 1b, an open-label, dose-escalation trial
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Under the guidance of MRI, the researcher injected NBIb-1817 into the bilateral putamen of 3 groups of patients (5 cases in each group).
The 3 groups used different doses: ≤7.
5×1011 vector genome (vg), ≤1.
5×1012 vg , ≤4.
7×1012 vg
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There were no reports of serious adverse events related to treatment in this trial
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The Parkinson's disease treatment drugs required for the two maximum dose groups were reduced by 21% to 30%
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During the entire 3 years, the motor function, changes, overall impression and quality of life of all 3 groups remained stable or improved
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The exercise fluctuation recorded in the diary improved in the two small-dose groups, but the maximum-dose group only improved at 12 months
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The most common adverse event was dyskinesia that occurred in 4 patients, which was relieved after adjustment of medication
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Comment on the safety of AADC gene therapy for Parkinson's disease during the 36-month follow-up period
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Although the efficacy of gene therapy is not as robust as some existing therapies (such as deep brain stimulation or carbidopa/levodopa enteric gel [Parkinsonism Relat Disord 2021; 83:132]), the results of this trial are promising and Lasting
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Commented articles Christine CW et al.
Safety of AADC gene therapy for moderately advanced Parkinson disease: Three-year outcomes from the PD-1101 trial.
Neurology 2021 Oct 14; [e-pub].
(https://doi.
org/ 10.
1212/WNL.
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