Next:Phase 1 Trial to Test BDNF Gene Therapy in Alzheimer’s Patients – Alzheimer’s News Today

A Phase 1 trial will evaluate the use of gene therapy in delivering brain-derived neurotrophic factor (BDNF) to the brains of people with Alzheimers disease or mild cognitive impairment (MCI), which often precedes dementia.

Researchers at the University of California San Diego (UCSD) School of Medicine are preparing to open a three-year trial in 12 people diagnosed with either with Alzheimers or MCI, according to a universitypress release. The release did not specify if eligible patients need to be at particular stages of Alzheimers.

The trial will assess the safety and efficacy of injecting the BDNF gene, carried on an engineered adeno-associated virus (AAV2), directly to certain brain regions in these 12 patients.

Another 12 people will serve as an untreated control group for comparison.

BDNF is a neurotrophin, a protein that promotes the growth and survival of both new and existing neurons. The protein also functions as a neurotransmitter, mediating communication between nerve cells.

It is active in several brain regions susceptible to degeneration over the course of Alzheimers. Past research has identified mutations in the BDNFgene that impair its signaling ability, and which associate with faster cognitive decline and a higher risk of developing Alzheimers.

The research team conducting the trial previously found that BDNF could prevent and reverse brain cell degeneration and death in rat, monkey, and mouse models of Alzheimers.

We found that delivering BDNF to the part of the brain that is affected earliest in Alzheimers disease the entorhinal cortex and hippocampus was able to reverse the loss of connections and to protect from ongoing cell degeneration, said Mark Tuszynski, MD, PhD, senior author of a 2009 study of this preclinical work.

The entorhinal cortex produces BDNF and functions as a hub for memory, navigation, and the perception of time. Although it normally produces BDNF throughout a persons life, people with Alzheimers tend to produce less of it.

The investigators plan to deliver the BDNF gene to patients via AAV2 because the BDNF protein is too large to cross the blood-brain barrier. The injections will be targeted to specific brain areas, as too much freely circulating BDNF can cause harmful side effects such as seizures.

UCSD has participated in past Alzheimers gene therapy trials, which used an AAV vector to deliver a different neurotrophin named nerve growth factor (NGF) to the brain. The university reports that data from one past trial showed increased nerve growth, the formation of new nerve connections, and activation of functional markers in participants brains.

Tuszynski believes that therapeutic BDNF represents an improvement over trials using NGF.

BDNF is a more potent growth factor than NGF for neural circuits that degenerate in [Alzheimers], he said. In addition, new methods for delivering BDNF will more effectively deliver and distribute it into the entorhinal cortex and hippocampus.

The upcoming trial will be the first to evaluate the use of AAV2BDNF in humans.

BDNFgene therapy has the potential, unlike other [Alzheimers] therapies currently under development, to rebuildbrain circuits, slow cell loss and stimulate cell function, Tuszynski said. We are looking forward to observing the effects of this new effort in patients with [Alzheimers] and MCI.

Anyone wanting more information on this Phase 1 trial can contact Michelle Mendoza at 858-822-7438 or by sending an email to [emailprotected].

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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Next:Phase 1 Trial to Test BDNF Gene Therapy in Alzheimer's Patients - Alzheimer's News Today