Journal ArticleDOI
A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease.
Michael S. Rafii,Tiffany L. Baumann,Roy A.E. Bakay,Jeffrey M. Ostrove,Joao Siffert,Adam S. Fleisher,Christopher D. Herzog,David Barba,Mary Pay,David P. Salmon,Yaping Chu,Jeffrey H. Kordower,Kathie M. Bishop,David Keator,Steven G. Potkin,Raymond T. Bartus +15 more
TLDR
Nerve growth factor is an endogenous neurotrophic‐factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimer's disease, but safe and effective delivery has proved unsuccessful.Abstract:
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.read more
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Design of virus-based nanomaterials for medicine, biotechnology, and energy
Amy M. Wen,Nicole F. Steinmetz +1 more
TL;DR: This review provides an overview of recent developments in "chemical virology", and surveys the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities.
Journal ArticleDOI
Current Clinical Applications of In Vivo Gene Therapy with AAVs.
Jerry R. Mendell,Jerry R. Mendell,Samiah Al-Zaidy,Louise R. Rodino-Klapac,Kimberly Goodspeed,Steven J. Gray,Christine N. Kay,Sanford L. Boye,Shannon E. Boye,Lindsey A. George,Stephanie Salabarria,Manuela Corti,Barry J. Byrne,Jacques P. Tremblay +13 more
TL;DR: This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity.
Journal ArticleDOI
Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality
Eloise Hudry,Luk H. Vandenberghe +1 more
TL;DR: The rationale, opportunities, limitations, and progress in clinical AAV gene therapy are discussed, particularly for nervous system disorders.
Journal ArticleDOI
Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease
TL;DR: It is hypothesized that a different pattern of neuronal loss will be found in the nbM of Lewy body disease brains of Parkinson’s disease as compared to AD, and the functional significance of the subregions of the nBM could prove important in elucidating the pathogenesis of dementia in PD.
Journal ArticleDOI
Adeno-Associated Virus-Based Gene Therapy for CNS Diseases
TL;DR: The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery.
References
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