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In their phase 1b open-label clinical trial, the PD-1101 investigators reported the 36-month safety and efficacy findings after bilateral putaminal infusions of an adenoviral vaccine for patients with advanced Parkinson disease (PD). The vaccine encoded the human aromatic amino acid decarboxylase (AADC) gene, which is responsible for converting levodopa to dopamine, and whose presence declines with time in PD as striatal neurons degenerate. The trial reported no adverse safety events. Participants who received the highest dose of the adenoviral AADC vector required 21%–30% lower doses of PD medications, and there were generally stable or improved outcomes across motor and quality of life assessments. Kang et al. highlight how dopamine and its metabolites may be toxic to certain neurons because they lack the intracellular machinery necessary to sequester dopamine. Although local infusion of the AADC adenoviral vector appears promising over the short term, the long-term consequences of this procedure warrant further exploration. Furthermore, the risk-benefit of this procedure will need to be studied in clinical trials that examine various combinations of therapies that are now available to patients with advanced PD.
In their phase 1b open-label clinical trial, the PD-1101 investigators reported the 36-month safety and efficacy findings after bilateral putaminal infusions of an adenoviral vaccine for patients with advanced Parkinson disease (PD). The vaccine encoded the human aromatic amino acid decarboxylase (AADC) gene, which is responsible for converting levodopa to dopamine, and whose presence declines with time in PD as striatal neurons degenerate. The trial reported no adverse safety events. Participants who received the highest dose of the adenoviral AADC vector required 21%–30% lower doses of PD medications, and there were generally stable or improved outcomes across motor and quality of life assessments. Kang et al. highlight how dopamine and its metabolites may be toxic to certain neurons because they lack the intracellular machinery necessary to sequester dopamine. Although local infusion of the AADC adenoviral vector appears promising over the short term, the long-term consequences of this procedure warrant further exploration. Furthermore, the risk-benefit of this procedure will need to be studied in clinical trials that examine various combinations of therapies that are now available to patients with advanced PD.
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Author disclosures are available upon request (journal{at}neurology.org).
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