BACKGROUND: Nerve growth factor (NGF) is an endogenous neurotrophic-factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimer's disease (AD), but safe and effective delivery has proved unsuccessful. METHODS: Gene transfer, combined with stereotactic surgery, offers a potential means to solve the long-standing delivery obstacles. An open-label clinical trial evaluated the safety and tolerability, and initial efficacy of three ascending doses of the genetically engineered gene-therapy vector adeno-associated virus serotype 2 delivering NGF (AAV2-NGF [CERE-110]). Ten subjects with AD received bilateral AAV2-NGF stereotactically into the nucleus basalis of Meynert. RESULTS: AAV2-NGF was safe and well-tolerated for 2 years. Positron emission tomographic imaging and neuropsychological testing showed no evidence of accelerated decline. Brain autopsy tissue confirmed long-term, targeted, gene-mediated NGF expression and bioactivity. CONCLUSIONS: This trial provides important evidence that bilateral stereotactic administration of AAV2-NGF to the nucleus basalis of Meynert is feasible, well-tolerated, and able to produce long-term, biologically active NGF expression, supporting the initiation of an ongoing multicenter, double-blind, sham-surgery-controlled trial.
BACKGROUND:Nerve growth factor (NGF) is an endogenous neurotrophic-factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimer's disease (AD), but safe and effective delivery has proved unsuccessful. METHODS: Gene transfer, combined with stereotactic surgery, offers a potential means to solve the long-standing delivery obstacles. An open-label clinical trial evaluated the safety and tolerability, and initial efficacy of three ascending doses of the genetically engineered gene-therapy vector adeno-associated virus serotype 2 delivering NGF (AAV2-NGF [CERE-110]). Ten subjects with AD received bilateral AAV2-NGF stereotactically into the nucleus basalis of Meynert. RESULTS:AAV2-NGF was safe and well-tolerated for 2 years. Positron emission tomographic imaging and neuropsychological testing showed no evidence of accelerated decline. Brain autopsy tissue confirmed long-term, targeted, gene-mediated NGF expression and bioactivity. CONCLUSIONS: This trial provides important evidence that bilateral stereotactic administration of AAV2-NGF to the nucleus basalis of Meynert is feasible, well-tolerated, and able to produce long-term, biologically active NGF expression, supporting the initiation of an ongoing multicenter, double-blind, sham-surgery-controlled trial.
Authors: William A Liguore; Jacqueline S Domire; Dana Button; Yun Wang; Brett D Dufour; Sathya Srinivasan; Jodi L McBride Journal: Mol Ther Date: 2019-08-05 Impact factor: 11.454
Authors: Casey A Maguire; Servio H Ramirez; Steven F Merkel; Miguel Sena-Esteves; Xandra O Breakefield Journal: Neurotherapeutics Date: 2014-10 Impact factor: 7.620
Authors: Kijung Sung; Luiz F Ferrari; Wanlin Yang; ChiHye Chung; Xiaobei Zhao; Yingli Gu; Suzhen Lin; Kai Zhang; Bianxiao Cui; Matthew L Pearn; Michael T Maloney; William C Mobley; Jon D Levine; Chengbiao Wu Journal: J Neurosci Date: 2018-02-26 Impact factor: 6.167
Authors: Mark H Tuszynski; Jennifer H Yang; David Barba; Hoi-Sang U; Roy A E Bakay; Mary M Pay; Eliezer Masliah; James M Conner; Peter Kobalka; Subhojit Roy; Alan H Nagahara Journal: JAMA Neurol Date: 2015-10 Impact factor: 18.302