February 4, 2013

Scientists have chosen three drugs to be tested as a way to prevent the onset of Alzheimer’s disease in people who are genetically predisposed to get the disease at an early age. If one or more of the medications prove to be effective, the hope is that they may also provide benefits for the millions more people at high risk of developing the far more common late-onset form of Alzheimer’s.

Current Alzheimer’s medications may ease symptoms for a time but do not stem the underlying progression of disease or prevent its onset. These new drugs, under investigation, are targeted at preventing the memory loss and thinking problems of Alzheimer’s from occurring in the first place. The study will be conducted at medical centers in the U.S., Europe and Australia starting in 2013.

“Trying to prevent Alzheimer’s symptoms from ever occurring is a new strategy,” says Dr. John C. Morris, a professor at Washington University School of Medicine, which is leading the study.

The study will test the drugs in 160 volunteers who have one of several genes that cause early-onset Alzheimer’s. People who inherit such genes typically begin to show signs of dementia at an early age, typically younger than 50. Carrying such genes leads to Alzheimer’s in 100 percent of cases, unlike the APOE gene that can raise the risk of late-onset Alzheimer’s but does not guarantee you will get the disease.

The three drugs undergoing testing are designed to combat the toxic effects of beta-amyloid, the toxic protein that builds up and forms plaques in the brains of those with Alzheimer’s. Each works in different ways. The drugs are:

*Gantenerumab, an antibody that attaches to beta-amyloid and helps to remove it from the brain.

*Solanezumab, which binds to beta-amyloid before it clumps together, inhibits  the plaque formation process.

* LY2886721, a drug that blocks an enzyme, beta-secretase, which is critical for beta-amyloid formation, thereby reducing the amount of beta-amyloid produced in the first place.

Earlier studies have shown them to be generally safe, with some hints that they may have benefits against Alzheimer’s. A recent analysis of data on solanezumab, for example, found that while the drug did not meet the study’s goals, it might slow memory loss in those with very mild Alzheimer’s.

For the prevention study, participants will be started on one of the three drugs, or a placebo, years before signs of memory loss or thought problems have appeared. At this early stage, the effects of the disease process on the brain are likely to be minimal. The hope is that by starting early, before brain damage has taken root, the drugs may stave off future development of symptoms. Eighty volunteers who do not have the genes will also participate as controls.

“In most trials in Alzheimer’s disease, people are treating the disease after the damage is being done to the brain,” said study leader Dr. Randall Bateman of Washington University. “And in this trial we’re trying to treat the disease before that damage gets done.”

Participants will receive scans and tests to look for signs of brain plaques and levels of beta-amyloid in the blood and spinal fluid. Such markers are an indication that Alzheimer’s disease is progressing, even if symptoms like memory loss are not evident. Scientists will monitor these markers to see whether the new treatments may be working to slow to stop the disease.

The first part of the trial, being conducted by a research partnership known as the Dominantly Inherited Alzheimer’s Network, or DIAN, is expected to last for two years. If it appears one or more of the drugs are working, volunteers will be switched to those drugs, and the trial will likely be expanded. For more information, visit www.Dian-Info.org.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Washington University School of Medicine. Dominantly Inherited Alzheimer’s Network (DIAN-Info.org).