Gene therapy may delay Alzheimer progression

Results from a preliminary eight-patient study of gene therapy for Alzheimer’s disease are positive enough to justify a larger clinical trial, Mark H. Tuszynski, M.D., Ph.D., reported April 27 at the 56th Annual Meeting of the American Academy of Neurology. Dr. Tuszynski says that a larger trial is being planned at a major medical center in Chicago.

The therapy involves genetically engineering some of a person’s skin cells so that they produce nerve growth factor, a chemical that plays a role in survival, repair and regeneration of the brain’s nerve cells. Researchers then inject the engineered cells into several brain regions severely affected by Alzheimer’s disease. In theory, nerve growth factor produced by the implanted cells improves the function of nerve cells and slows their decline, thus delaying Alzheimer progression.

Although the purpose of this study was to assess safety rather than effectiveness, results suggest not only that the procedure is safe if administered under general anesthesia but also may offer some benefit. A year and a half after treatment, participants experienced mental decline at a rate that was slower than before their surgery as well as less than the average expected rate.

In addition, imaging with positron emission tomography (PET) showed increased brain activity in treated individuals compared with untreated individuals with Alzheimer’s disease.

"These results need to be interpreted with cautious optimism because the study is so small,” says William H. Thies, Ph.D., Alzheimer’s Association vice president, Medical and Scientific Affairs. “The course of Alzheimer’s disease varies tremendously in the early stages, and with only eight individuals it’s really impossible to tell whether the benefit was due to the treatment or natural fluctuation in symptoms.”

"Another issue,” Thies notes, “is that the treatment here is a neurosurgical procedure that may not be practical to perform on the millions of older adults with Alzheimer’s disease. If the benefit is borne out in a larger trial, though, it may revive interest in other strategies for getting nerve growth factors into the brain. There are drugs that can stimulate the brain’s own production of these factors, but development stalled out after mixed results from early clinical trials. Proof-of-concept through gene therapy could renew interest in those pharmaceutical approaches.”