UCSD Health Sciences UCSD Health Sciences
December 10, 1999

Media Contact: Leslie Franz (619)543-6163


Patient trials of an experimental gene therapy for early stage Alzheimer's disease will move forward, following review by the Recombinant DNA Advisory Committee (RAC), which met this week in Bethesda, Maryland. The stage is now set for the first patients to be treated in spring 2000.

RAC, an advisory board to the National Institutes of Health, today reviewed a proposal submitted by Mark Tuszynski, M.D., Ph.D., associate professor of neurosciences at the UCSD School of Medicine and neurologist with the Veterans Affairs San Diego Health Care system. As an advisory board, RAC does not take action, but their review is an important step in the process of launching a patient trial involving the transfer of genes to humans.

Based on successful studies in rhesus monkeys, Tuszynski plans to insert genetically altered tissue into the brains of individuals diagnosed with early Alzheimer's disease, with memory loss as their primary symptom. The first phase of this study, approved by the Food and Drug Administration in October, will enroll only eight patients, and will focus on the safety of this approach.

Tuszynski and a team of UCSD, Salk Institute and UC Davis scientists reported in September the dramatic restoration of atrophied brain cells in aged rhesus monkeys after insertion of tissue genetically altered to produce nerve growth factor directly into the subcortical region of the brain. With the elevated levels of nerve growth factor, cells that had shrunk and ceased functioning by 43 percent of normal levels due to normal aging were restored to within 92 percent of normal function. These results were published in the September 14 Proceedings of the National Academy of Sciences.

“We have shown in monkeys that this procedure has a measurable impact on the normal older brain, restoring cells that are important in mental functioning,” said Tuszynski. “In order to study whether this procedure actually slows or reverses the mental decline associated with Alzheimer's disease, which involves the same brain cells studied in monkeys, we have to now study human patients, since no animals actually suffer from Alzheimer's disease.”

With this review complete, Tuszynski and his team, which in includes Hoi-Sang U, M.D., professor of surgery at UCSD and chief of neurosurgery at the VA San Diego Medical Center, will now begin screening patient volunteers to participate in this study.

According to Tuszynski, screening will be rigorous. Only patients with a firm diagnosis of Alzheimer's disease, but still in the early stages of the disease and able to understand the experimental procedure and give their consent, will be enrolled in this first phase.

For this trial, skin cells altered to contain the gene for nerve growth factor will be inserted through a needle into the part of the brain that regulates memory, attention, and other important brain functions. The patients will be monitored closely over time, primarily to ensure the safety of this procedure. It is possible that the patients will demonstrate some beneficial response to the therapy in their cognitive function as well, Tuszynski said, although such results are not a specific goal of this phase of the clinical trial.

RAC was established in 1974 to advise the NIH on the safety and risks of using recombinant DNA techniques. About one-third of the 15-member board consists of non-scientist members, with the other two-thirds of the members representing scientific institutions and universities from throughout the country. The committee's major role is to evaluate clinical trials that involve the transfer of recombinant DNA into humans. UCSD's own institutional review board, the Human Subjects Committee, also has approved the protocol and will be responsible for day-to-day oversight of the trial.