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Physicians Update

 
Spring 2012

National Research Effort Underway to Combat Alzheimer’s Disease

An estimated 5.4 million people in the United States live with Alzheimer's disease, double the number since 1980. Absent a prevention strategy or cure, the current figure is expected to double again before the middle of this century as the population ages, with staggering human and financial burdens on patients, their families and society.

"There is a clear need for research to find a way to address this cost and human toll," says Joshua Grill, Ph.D., director of the Katherine and Benjamin Kagan Alzheimer's Disease Treatment Development Program and a member of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA. The good news, Dr. Grill says, is that an intensive national effort is beginning to bear fruit.

Several experimental treatments have either just completed Phase 3 clinical trials or are at the late stage - including, potentially, the first disease-modifying therapies for Alzheimer's.

Current FDA-approved treatments, which include three acetyl cholinesterase inhibitors and the drug memantine, help relieve symptoms but don't affect the underlying biology of the disease or slow the rate of cognitive deterioration, Dr. Grill notes. Thus, research efforts, including many at UCLA, have focused on better understanding the disease as a way to identify targets that alter the natural history of Alzheimer's disease. "If either of the treatments whose results are expected to be announced at the end of this year is capable of doing that, it will represent a major step," Dr. Grill says.

Today's clinical trials are building on laboratory discoveries made over the last several decades, most notably the molecular changes leading to the formation of the plaques and tangles that develop in the brains of people with Alzheimer's disease, Dr. Grill notes. "Some of the most promising drugs aim to interrupt the cascade of events that result in the formation of those plaques and tangles," he explains.

The drugs closest to approval are immunotherapies - antibodies against the protein that accumulates in the plaques. "There are multiple antibodies being developed that have demonstrated an ability to reduce the plaque in the brain of someone with Alzheimer's disease," Dr. Grill says. "That's something we've never had before."

Also moving through clinical trials are inhibitors for the enzymes critical to the formation of the plaques. Neuroprotective strategies are also being tested. An ongoing gene-therapy study at UCLA and nine other centers nationwide injects the brain with human DNA for nerve growth factor, which is known to keep neurons healthy in the developing brain. In addition to the increased activity around promising drug strategies, many clinical trials are enrolling patients at an earlier stage - before they meet the criteria for dementia - in an effort to stave off the disease before it is clinically manifest.

With the possibility of disease-slowing drugs becoming available in the foreseeable future, much research effort also is being invested in finding ways to identify people at the earliest sign of cognitive impairment - or, ideally, even before they have developed symptoms. "There are many studies suggesting that biological signs of Alzheimer's disease begin perhaps a decade before memory starts to worsen," Dr. Grill says. "It may be particularly important to be able to start disease-modifying drugs as early as possible, to potentially arrest disease progression at its earliest stages. There could be a time in the future when people might be screened for signs of Alzheimer's disease at certain ages, so that these drugs can be started to prevent symptoms from developing."

"This is an exciting time," Dr. Grill says. "There is tremendous energy being put into better understanding the disease, diagnosing it earlier, and finding treatments that can help slow and potentially prevent it from occurring."





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