Gene Therapy an Effective Treatment for Alzheimer's

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Nerve growth factor (NGF) gene therapy may be a promising treatment for neurodegenerative disorders, according to postmortem findings from a long-term trial.

Mark H. Tuszynski, MD, PhD, of the University of California, San Diego, and colleagues initiated a clinical trial of NGF in patients with Alzheimer’s disease in 2001 with a goal of determining whether or not NGF could prevent or reduce cholinergic neuronal degeneration in Alzheimer’s. The study, published in JAMA Neurology, documents the postmortem findings in 10 patients with survival times from one to 10 years after treatment.

During the clinical trials, which ran from March 2001 to October 2012, 10 patients with Alzheimer’s underwent NGF gene therapy using ex vivo (n=8) or in vivo (n=2) gene transfer. Degenerating neurons in all 10 patients were found to respond to NGF, with axonal sprouting toward the NGF source. In three patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred in the NGF-treated side of the brain.

Additionally, two patients, who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer, were found to have activation of cellular signaling and functional markers. Neurons that exhibited tau pathology and those free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes, resulting in activation of cell signaling. No adverse pathological effects related to NGF treatment were observed.

The results confirm that degenerating neurons remain able to respond to growth factors with axonal sprouting, cell hypertrophy, and activation of functional markers. NGF-induced sprouting persisted for 10 years post-transfer. NGF gene therapy, which appeared safe over extended periods, should be further tested for the treatment of neurodegenerative disorders.

Gene Therapy an Effective Treatment for Alzheimer's
Research shows that degenerating neurons remain able to respond to growth factors after the onset of Alzheimer's.

Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment.

Mark H. Tuszynski, MD, PhD, of the University of California, San Diego, and colleagues hoped to determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset.

READ FULL ARTICLE From archneur.jamanetwork.com
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