Gene therapy trial for AD demonstrates safety and efficacy

By Laura Newman

NEW YORK (Reuters Health) - The first human gene therapy efforts in adults with neurodegenerative brain disorder has produced promising results, according to researchers.

They report on 10 patients with early Alzheimer's disease treated with nerve growth factor gene therapy, in a paper online August 24 in JAMA Neurology.

"Every brain showed a growth response, with axonal sprouting that lasted at least seven years," Dr. Mark Tuszynski, director of the Translational Neuroscience Institute at the University of California, San Diego in La Jolla, told Reuters Health. "This is the largest pathological examination of brains in patients undergoing gene therapy."

"It's safe and well tolerated," he added, noting that the growth factors don't penetrate the blood-brain barrier.

Dr. Tuszynski pointed out that amyloid therapies for Alzheiner's disease have been disappointing. This new strategy, he believes, may someday offer a sustainable, long-term treatment for this and other neurodegenerative diseases, also obviating the need to take daily medicine.

"Ten patients with early AD underwent nerve growth factor gene therapy using ex vivo or in vivo gene transfer," the researchers wrote. "The brains of all eight patients in the first phase 1 ex vivo trial and of two patients in a subsequent phase 1 in vivo trial were examined."

All ten patients showed a growth response to nerve growth factor in degenerating neurons. Axons sprouted close to where the nerve growth factor was delivered. The sprouting was durable ten years after gene transfer. In three patients who had unilateral gene transfer, the researchers found cholinergic neuronal hypertrophy on the treated side, in contrast to the untreated side.

The researchers observed no adverse side effects.

Dr. Jude Saluski, director of the Gene Therapy Center, University of North Carolina, Chapel Hill, praised the work. "The studies show that this approach proves capable of infecting and producing the gene product in both normal and diseased cells," he said in a telephone interview with Reuters Health.

"Thus, the potential exists to correct the diseased cells in Alzheimer's," he added. "Finally, the findings demonstrate that, indeed, the vector-derived (nerve growth factor) exerted the expected effects in the central nervous system, so the gene product is active. This demonstration of vector efficacy and safety clearly encourages further studies focused on achieving a significant therapeutic effect."

The National Institutes of Health, the Veterans Health Administration, and the Alzheimer's Association supported this research. Dr. Tuszynski is the scientific founder of Ceregene, but he no longer has a financial interest in the company.

SOURCE: https://bit.ly/1fIUH3B

JAMA Neurol 2015.