Growth Factor Gene Therapy for Alzheimer’s Disease

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Tuszynski, Mark H.^{a; b; *}

Affiliations: [a] Department of Neurosciences, University of California San Diego, La Jolla, CA, USA | [b] Veterans Affairs Medical Center, San Diego, CA, USA

Correspondence: [*] Correspondence to: Mark H. Tuszynski, MD, PhD, Department of Neurosciences, 0626, University of California San Diego, La Jolla, CA 92093, USA. E-mail: [email protected].

Abstract: Nervous system growth factors are natural proteins of the brain that influence neuronal survival and function throughout life, from embryonic development to old age. In animal models of Alzheimer’s disease (AD), the growth factor brain derived neurotrophic factor (BDNF) prevents neuronal death, activates neuronal function, builds new synapses and improves learning and memory. Accordingly, we are determining whether gene delivery of BDNF in patients with AD will slow disease progression and improve memory. In a previous clinical trial of nerve growth factor (NGF) gene therapy in AD patients (NCT00017940, June 2001), we learned that growth factors can unequivocally elicit classic trophic responses from degenerating neurons in AD. Experience gained from the earlier NGF gene therapy trial is guiding our effort to optimize gene delivery of BDNF in our present clinical program (NCT05040217, June 2021).

Keywords: Alzheimer’s disease, brain derived neurotrophic factor, clinical trial, gene therapy, intraparenchymal, intrathecal, mild cognitive impairment, MRI guidance, nerve growth factor, systemic

DOI: 10.3233/JAD-240545

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S433-S441, 2024