Drug Offers a Ray of Hope for Alzheimer’s Patients

Photo courtesy Alzheimer's Association

This is the first of a five-part special report on Alzheimer’s. Check back next week for breaking news from the international conference on Alzheimer's.

Dimebon—a new drug for Alzheimer’s disease whose promising test results were reported with great fanfare earlier this month—will make even more news next week at an international Alzheimer’s conference in Chicago.

According to a study published in the journal Lancet on July 19, Dimebon was shown to improve thinking and behavior for a year in people with mild to moderate forms of the disease. At the Alzheimer’s Association four-day conference that begins Sunday, researchers will disclose whether the drug’s benefits continued when that study was extended to 18 months.

Dimebon will be among half a dozen new therapies—from a food supplement to two new medicines that attack the disease in a totally new way—whose latest test results will be made public for the first time at the conference, where more than 5,000 scientists from 60 countries will gather.

Research is going full throttle on this devastating disease on a number of fronts and “things are breaking right and left now,” says Sam Gandy, M.D., associate director of the Mount Sinai Alzheimer’s Disease Research Center in New York, who chairs the National Medical and Scientific Advisory Council of the Alzheimer’s Association.

Dimebon, a small molecule that appears to help protect brain cells against the ravages of Alzheimer’s, “was good news we didn’t expect,” he says.

Today, the few drugs available to treat Alzheimer’s only tend to stabilize impaired memory and thinking for a time, “and then the decline resumes at the same rate as before,” Gandy says.

“With Dimebon, people actually seemed to get better at the beginning—and that’s an advance, that’s real news—and once they got better, they stayed better for up to a year,” he says. “The drug sustained the improvements at a plateau. So we’re really keen to see the 18-month data to see if the drug continues its benefits.”   

The drug, an unlikely contender for an Alzheimer’s breakthrough, is an antihistamine, which has been used in Russia since 1983—for hay fever. It was a Russian chemist who first explored its potential with dementia, and now final human trials of the drug are under way around the world.

Lucky Break?

“Part of science is designing the perfect experiment,” Gandy says, “and part is recognizing something exciting when you stumble on it, and this is in the latter category.”

If the good news about Dimebon was unexpected, it was certainly welcome—especially in light of the recent, painful failures of two highly promising Alzheimer’s drugs, Alzhemed and Flurizan.

Rather than treat the symptoms of Alzheimer’s, those drugs sought to attack amyloid, the sticky plaque that forms around the brain cells of Alzheimer’s patients. Although the causes of Alzheimer’s are not fully understood, scientists have repeatedly shown that when plaque is reduced in the brains of mice with the disease, the mice can solve problems and run mazes that once confounded them.

The failure of the two promising anti-amyloids to improve memory and cognition in clinical trials has scientists reviewing the amyloid hypothesis.

“What I’m concerned about now,” says Gandy, “is that we may need to get in with the anti-amyloid medicines earlier than we thought, maybe even before there are even symptoms of the disease, in order for the drugs to work.”

He says it may be that once the amyloid has developed, Alzheimer’s has taken hold, so “even if you remove the amyloid, the disease keeps going. That’s what we’re concerned about now.”

Amazing Results

Along with Dimebon, one of the most anticipated reports will come from Australian researchers who conducted a human trial with the experimental drug dubbed PBT2—which quickly and profoundly improved cognition in mice with Alzheimer’s. In the mice studies the drug was shown to reduce the toxic form of amyloid by preventing its interaction with zinc and copper. “The results with the mice were amazing.” says Gandy. “And I’m really excited to see what the clinical data is from the human study.”

While much of the current research has been aimed at preventing, blocking or eliminating amyloid plaque that collects between brain cells, researchers at the Chicago conference will report on human test results of the first therapies to attack the tangles, made of short fragments of a protein called tau, that form inside those brain cells. Scientists believe that by targeting the tangles, they may be attacking the disease earlier in its development.

“With these new therapies, we are moving downstream from amyloid to ...  the tangles that we think begin the neurogeneration, the death of the nerve cell,” Gandy says.    

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Researchers will also report on their progress in developing tests to diagnose Alzheimer’s and on methods to track its progress in the human brain through new imaging techniques, information that is key to successful treatment of the disease. Other studies will report on how marital status and exercise affect the risk of Alzheimer’s and the best most effective way to talk to Alzheimer’s patients.