Gene therapy rescues brain cells from Alzheimer’s

The Guardian reports on a new therapy – nerve growth factor – that effectively saves dying brain cells:

The new results are preliminary findings from the very first human trials designed to test the potential benefits of nerve growth factor (NGF) gene therapy for Alzheimer’s patients.

NGF was discovered in the 1940s by Rita Levi-Montalcini, who convincingly demonstrated that the small protein promotes the survival of certain sub-types of sensory neurons during development of the nervous system. Since then, others have shown that it also promotes the survival of acetylcholine-producing cells in the basal forebrain, which die off in Alzheimer’s.

In 2001, Mark Tuszynski and his colleagues at the University of California, San Diego School of Medicine launched a clinical trial based on these findings.

In phase I of this trial, eight patients with mild Alzheimer’s Disease received ex vivo therapy to deliver the NGF gene directly into the brain. This involved first taking a skin biopsy from the patients’ backs, isolating connective tissue cells called fibroblasts, genetically modifying them to express the NGF genes, and then implanting the cells into the patients’ basal forebrain.

The latest results come from post-mortem examination of these patients’ brains, all of whom had also been recruited in a safety trial between March 2001 and October 2012, plus those of two others, who had received in vivo therapy, involving injection of a modified virus carrying the NGF gene into the basal forebrain, in a subsequent phase I trial.

Some of the participants died about one year after undergoing therapy, and others survived for 10 years after the treatment. But the autopsies revealed that all of them had responded to the treatment – all the brain tissue samples taken from around the implantation sites contained diseased neurons, as expected, but the cells were overgrown, and had sprouted axonal fibres that had grown towards the region into which NGF had been delivered. By contrast, cells in samples taken from the untreated side of the brain exhibited no such response.