$5M Grant Supports Phase 1 Trial of AAV2-BDNF, Potential Gene Therapy

The National Institute on Aging (NIA) has awarded a five-year grant worth up to $5 million to support a clinical trial that will test AAV2-BDNF, an investigational gene therapy, in people with Alzheimer’s disease or mild cognitive impairment, which often precedes dementia.

The therapy aims to deliver the gene BDNF to cells within specific regions of the brain by using an engineered adeno-associated virus (AAV2). This would prompt the cells to “read” the gene and produce the BDNF protein.

BDNF, short for brain-derived neurotrophic factor, is a growth factor found in the brain and other parts of the nervous system. As its name suggests, this protein sends signals that support the survival of existing neurons (nerve cells), as well as promoting the growth of new neurons and the formation of new synapses (connections between individual neurons).

“We found in earlier studies that delivering BDNF to the part of the brain that is affected earliest in Alzheimer’s disease — the entorhinal cortex and hippocampus — was able to reverse the loss of connections and to protect from ongoing cell degeneration” in animal models,  Mark Tuszynski, MD, PhD, a professor of neuroscience and director of the Translational Neuroscience Institute at the University of California San Diego (UCSD) School of Medicine, said in a university press release.

Of note, the entorhinal cortex normally produces BDNF, although this production tends to be decreased in Alzheimer’s patients. Both the entorhinal cortex and the hippocampus play central roles in processing memory.

Researchers at UCSD will test the therapy over three years in Phase 1 clinical trial. Twelve people diagnosed with either Alzheimer’s or mild cognitive impairment will get the investigative treatment, another 12 will not, and will serve as controls for comparison.

According to Tuszynski, the trial’s lead investigator, the study has already begun enrolling participants, but multiple slots still remain available. Interested individuals can get more information on the trial by contacting Michelle Mendoza at 858-534-8857 or by emailing [email protected].

Tuszynski noted that delivering BDNF to the brain has advantages over another growth factor that has been explored in Alzheimer’s gene therapy, nerve growth factor (NGF).

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

In addition to the NIA, a part of the National Institutes of Health, the trial is supported by funding from the Alzheimer’s Association and from the philanthropist Darlene Shiley.