Postmortem findings hint at Alzheimer's gene therapy effect

An experimental gene therapy used in patients with Alzheimer's disease appears to slow down neural degeneration.

The preliminary findings are based on the post-mortem brains of patients with Alzheimer's disease who participated in a phase I clinical trial to test the safety of the treatment, running between 2001 and 2012 at the UC San Diego. The study was designed to assess whether nerve growth factor (NGF) — a protein that occurs naturally in our bodies and is essential for cell growth, maintenance and survival — might safely slow or reduce the spread of brain-cell death in Alzheimer's disease.

The results confirm earlier findings that none of the patients suffered adverse effects, but also showed that all the patients had responded to treatment, suggesting NGF had been taken up by the brain cells. Degenerating neurons showed signs of axonal sprouting (an indication of neuronal repair and recovery) in all ten of the Alzheimer's disease brains studied. This was true even in brains that had been given the gene therapy ten years previously.

'All of the Alzheimer's disease brains showed anatomical evidence of a growth response to the growth factor,' said the principal investigator, Professor Mark Tuszynski, of the UC San Diego Translational Neuroscience Institute and the VA Medical Center, San Diego. 'This means that growth factors as a class consistently result in activation of dying cells in human neurodegenerative disorders.'

Eight of the patients in the study had ex-vivo gene therapy, where a skin biopsy was taken from each patient and genetically modified so that the cells expressed NGF, before being injected directly into the brains of the patients.

The remaining two patients had in-vivo therapy, where a modified virus carrying NGF was injected into the brain, where it altered the cells so that they too expressed NGF. Both strategies involved injections straight into the brain because NGF is too big to cross the blood-brain barrier; an injection elsewhere in the body would not have affected the brain.

Phase II trials testing the efficacy of the treatment are currently ongoing, and results from these trials will be crucial. It remains to be seen whether the effects seen in the brain have any effect on disease symptoms such as memory loss and mental function.

Results of the study were published in JAMA Neurology.