Movement disorders : official journal of the Movement Disorder Society · 2026
A Phase 1 Study of Convection-Enhanced Delivery of Intraputaminal AAV2-GDNF in Advanced Parkinson's Disease.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Heiss John D, Ehrlich Debra J, Lungu Codrin, Choi Joseph Y, Scott Gretchen, Dustin Irene, Hammoud Dima A, Herscovitch Peter, Lonser Russell R, Zaghloul Kareem A, Bankiewicz Krystof
Аннотация
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Neurotrophic therapeutic approaches have been limited in part by incomplete delivery to the putamen. We developed image-guided convection-enhanced delivery with real-time monitoring to improve intraputaminal distribution of neurotrophic gene therapy.
OBJECTIVES: To evaluate the 5-year safety and tolerability of bilateral putaminal delivery of adeno-associated virus serotype 2 encoding glial cell line-derived neurotrophic factor (AAV2-GDNF), and to describe exploratory long-term clinical outcomes.
METHODS: This was a single-center, open-label, phase 1, dose-escalation study in adults with advanced PD. Thirteen participants received bilateral putaminal infusions across three dose cohorts (six low-dose, six medium-dose, one high-dose) and were followed for 5 years. Adverse events, including serious adverse events, were collected, and their relationship to the study agent was determined. Longitudinal clinical outcomes were analyzed with a mixed-effects model.
RESULTS: Across follow-up, 562 adverse events were recorded; 45 were considered possibly or probably related to the study drug. The 13 serious adverse events that occurred were not attributed to the study drug. One participant died 45 months after infusion from aspiration pneumonia following cervical spine surgery at an outside institution. The study drug had a mean putaminal coverage of 26% ± 10%. Exploratory clinical measures did not change significantly between baseline and final follow-up.
CONCLUSIONS: Bilateral putaminal neurotrophic gene therapy delivered with real-time image guidance was well tolerated over 5 years, without protocol-defined stopping events. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
OBJECTIVES: To evaluate the 5-year safety and tolerability of bilateral putaminal delivery of adeno-associated virus serotype 2 encoding glial cell line-derived neurotrophic factor (AAV2-GDNF), and to describe exploratory long-term clinical outcomes.
METHODS: This was a single-center, open-label, phase 1, dose-escalation study in adults with advanced PD. Thirteen participants received bilateral putaminal infusions across three dose cohorts (six low-dose, six medium-dose, one high-dose) and were followed for 5 years. Adverse events, including serious adverse events, were collected, and their relationship to the study agent was determined. Longitudinal clinical outcomes were analyzed with a mixed-effects model.
RESULTS: Across follow-up, 562 adverse events were recorded; 45 were considered possibly or probably related to the study drug. The 13 serious adverse events that occurred were not attributed to the study drug. One participant died 45 months after infusion from aspiration pneumonia following cervical spine surgery at an outside institution. The study drug had a mean putaminal coverage of 26% ± 10%. Exploratory clinical measures did not change significantly between baseline and final follow-up.
CONCLUSIONS: Bilateral putaminal neurotrophic gene therapy delivered with real-time image guidance was well tolerated over 5 years, without protocol-defined stopping events. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.