Drugs Aim to Attack Root of Alzheimer's
Scientists try to move beyond just treating symptoms
WEDNESDAY, July 21, 2004 (HealthDayNews) -- The only drugs currently available for Alzheimer's disease are ones that boast only a "modest" impact on symptoms.
The next major shift in research, one that is under way now, is toward therapies that attack the root causes of the disease.
Three studies being presented this week at the International Conference on Alzheimer's Disease and Related Disorders in Philadelphia report progress in this area.
"It's definitely an advance in the field that the major thrust is on the development of disease-modifying treatments rather than treatments for symptomatic benefits," said Steven Ferris, director of the Alzheimer's Disease Center at the Silberstein Institute for Aging and Dementia at New York University Medical Center.
It's widely agreed that the cause of Alzheimer's, or at least an important effect of the cause, is the accumulation of protein called beta-amyloid in the brain, Ferris explained. Approaches to attacking the root cause include clearing away the accumulations, or "plaques," after they have formed; preventing the protein pieces from forming plaques; and stopping the forming of the protein in the first place by interfering with the amyloid precursor protein that produces beta-amyloid when it is cut into smaller pieces.
One trial being presented at the conference, which runs from July 17 to 22, found a drug called Alzhemed was safe and well-tolerated in 58 patients with Alzheimer's. The drug interferes with the ability of proteins to stick together.
Alzhemed was also found in the cerebrospinal fluid (CSF) of participants, meaning it bridged the blood-brain barrier. Also, circulating levels of beta-amyloid protein in the CSF were lowered after the three-month trial.
Thus far in the trial, "we were able to establish that the drug is safe, that it gets into the brain, and that it reduces amyloid levels, so the results are very encouraging," said study author Dr. Paul Aisen, a professor of neurology and medicine and director of the Memory Disorders Program at Georgetown University Medical Center in Washington, D.C.
The researchers have now launched a final phase of the trial, involving 950 participants at 70 sites across the United States and Canada. That trial will last 18 months, meaning results will likely be available in three to four years. Ideally, the drug would be used to treat people in the extremely preliminary stages of the disease to prevent progression into full-blown Alzheimer's, Aisen said.
The current study, while important, is small and of short duration, Ferris warned. "There's a hint that it's doing what it's supposed to do, but it's not a big enough study or a long enough study where you would expect to see any clinical effect," he said.
A second trial, sponsored by Eli Lilly & Co., tried to prevent beta-amyloid from forming by disrupting enzymes called secretases. These enzymes are responsible for cutting amyloid precursor protein into the smaller beta-amyloid. The drug was tested in 37 healthy adults for 14 days and showed no significant side effects. The drug also seemed to reduce beta-amyloid levels in the blood.
In yet another study, researchers at Merck & Co. reported on a test compound that they think may have potential to stop the formation of beta-amyloid by interfering with another enzyme, beta-secretase.
Another drug, phenserine, is in late-stage trials in Europe, Ferris added. This drug is a cholinesterase inhibitor, one of the class of drugs currently approved for symptomatic relief, but it also seems to be able to inhibit the production of beta amyloid.
The Alzheimer's Association has information on treatments for the disease.