Gene Therapy for Alzheimer's Disease - Clinical Trial Updates

Update January 25, 2008

Nerve Growth Factor (NGF) stimulates the function and prevents the death of an important cell type in the brain that degenerates in Alzheimer’s disease (the “cholinergic neuron”). In animal studies, NGF improves memory and prevents degeneration of cells resulting from injury, overproduction of amyloid, or aging.

To determine whether NGF can prevent cell death and improve cognitive function in Alzheimer’s disease, we began a clinical program of NGF gene transfer to humans with Alzheimer’s disease in 2001. In 2005, results from the first eight people with early Alzheimer’s disease who underwent NGF gene transfer were reported in the journal Nature Medicine (2005; Volume 11, p 551-555).

Two patients in the trial who were sedated but not anesthetized moved as the NGF genetic material was injected into the brain, causing bleeds; subsequent injections into patients were therefore performed under general anesthesia and were completed without complication. After an average follow-up period of 22 months, no long-term adverse effects of NGF occurred.

Evaluation of two commonly used cognitive tests in Alzheimer’s disease, the Mini-Mental Status Examination and the Alzheimer Disease Assessment Scale, revealed slowing of the disease by 36–51% in treated patients. However, it should be noted that a placebo group was not studied, and it is therefore possible that these potential clinical benefits were simply a “placebo effect”. Serial PET scans demonstrated significant increases in cortical brain metabolism after treatment. Examination of the brains of four people from the trial who have come to autopsy by January 2008 demonstrates clear cell growth in response to NGF in the human brain. We conclude from this preliminary study that additional clinical trials of NGF for Alzheimer’s disease are warranted.

Another clinical trial of NGF gene therapy was performed at Rush University in Chicago, beginning in 2005. That trial used a newer generation gene therapy “vector” to administer NGF more potently to people with Alzheimer’s disease. To date, there have been no significant safety problems in 6 people who underwent the clinical study at Rush. The trial is currently enrolling additional patients at the University of California – San Diego, in the Shiley-Marcos Alzheimer’s Disease Research Center. Information regarding the trial is available at 858-622-5800.

A Phase 2 multi-center trial of NGF gene therapy is scheduled to begin later in 2008. The trial will include a placebo group and will be performed in a larger number of people, allowing a more clear understanding regarding the potential ability of NGF to treat Alzheimer’s disease. Several medical centers around the country will enroll people into the trial. The Phase 2 trial will be led by Paul Aisen, M.D., of the University of California – San Diego. Information regarding the trial is available at 858-622-2028.

Today, we do not yet know whether NGF will be a useful treatment for Alzheimer’s disease. NGF is a potent treatment for preventing the death of neurons in the brains of rats and monkeys; the current clinical trials will determine whether NGF will also exert these beneficial effects in humans with Alzheimer’s disease.