Nerve growth factor ( NGF ) gene therapy may slow the rate of cognitive decline in patients with Alzheimer’s disease and increase metabolic activity in the brain.

Cholinergic neuron loss is a cardinal feature of Alzheimer’s disease.

Nerve growth factor ( NGF ) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging.

Researchers from University of California San Diego ( UCSD ) performed a phase 1 trial of ex vivo NGF gene delivery in eight patients with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain.

Cognitive outcomes were assessed in the six patients who completed the NGF delivery procedure.
The Mini Mental Status Examination ( MMSE ), which evaluates cognitive function, was administered at screening, the time of treatment and at several intervals after treatment.
Over an average post-treatment follow-up period of 22 months, the rate of decline on the MMSE among NGF-treated patients was reduced by as much as 51 percent.
An additional test, Alzheimer's Disease Assessment Scale-Cognitive Subcomponent ( ADAS-Cog ), also showed improvements in rates of decline followed the MMSE findings.

Post-operative PET scans in four patients showed significant increases in the brain's absorption of a radioisotope 18-fluorodeoxyglucose, an indicator of increased metabolic activity in the brain.
The researchers noted that the increase was observed in most cortical regions that receive cholinergic input from forebrain nerve cells called the nucleus basalis, and in the cerebellum, a structure associated with cortical plasticity.

Brain autopsy from one patients suggested robust growth responses to NGF.

Source : Nature Medicine, 2005


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