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Three Drugs to Be Tested to Stave Off Alzheimer’s

Scientists have selected three different types of Alzheimer’s drugs to be tested in the first large-scale international attempt to prevent the disease in people who are otherwise doomed to get it.

It is one of three studies with the same goal that will start early next year. This one involves 160 people from the United States, Britain and Australia with a variety of gene mutations that cause Alzheimer’s with absolute certainty. Most of the test subjects will have no symptoms yet of the degenerative disease that ravages the brain, destroying memory and thought. But they would be expected to start showing signs of problems with memory and thinking within five years unless the drugs work. The hope is that by intervening early, the disease might be headed off.

Another study starting next year involves an extended family in Colombia that shares the same mutation. Anyone who inherits that mutated gene get Alzheimer’s disease. A third study will involve people in the United States age 70 and older who seem perfectly healthy and who do not have any known Alzheimer’s mutations but in whom, brain scans show, the disease is starting to manifest itself.

In recent years, as studies involving people who already have Alzheimer’s have failed, researchers increasingly have called for studies in those who do not yet have the disease, arguing that the time to intervene is before the brain is irreversibly damaged. So the new study with people who are destined to get Alzheimer’s unless a drug can stop it is a way to test that idea.

 “It’s an exciting opportunity,” said Dr. Ronald Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic, who is not involved with the study.

Maria C. Carrillo, vice president of medical and scientific relations at the Alzheimer’s Association, said the results would come quickly. Within a few years, as researchers simultaneously compare the three approaches to stopping the disease, they should know which drug, if any, is going to work. The association contributed $4.2 million to the study, more than twice as much as it has ever spent on a grant, Dr. Carrillo said.

The announcement comes at a time of transition for Alzheimer’s research. In recent years, investigators have discovered methods of spotting and tracking the progression of the disease before any clinical symptoms appear, using brain scans and spinal taps and sensitive tests of memory. They have led to what many think is the start of a new era in which drugs can be assessed without waiting for effects on profound symptoms.

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Dr. Randall Bateman is the lead researcher in the study.Credit...Jennifer Silverberg for The New York Times

That is a goal of the study whose drugs were announced on Wednesday. Known as DIAN TU, for Dominantly Inherited Alzheimer’s Network Trials Unit, it was designed to get the most information possible in as short a time as possible. Three-quarters of the subjects will get one of three drugs aimed at beta amyloid, a protein that forms the hard, barnaclelike plaques on the brain that are the hallmark of Alzheimer’s.

The drugs were chosen from among 15 that drug companies offered, said the study’s principal investigator, Dr. Randall Bateman of the Washington University School of Medicine in St. Louis. A committee assessed them, looking for drugs with the best evidence of effectiveness and the least likelihood of dangerous side effects. One concern is something called ARIA, for amyloid related imaging abnormality. People with the abnormality may have no signs that anything is wrong, but brain scans show what looks like a change in neural connections. ARIA is a rare side effect of some experimental Alzheimer’s drugs, and it is not clear what it means, but it is a concern and will be monitored closely, Dr. Bateman said.

For the first two years of the study, researchers will follow the subjects with scans and memory tests, looking for signs that the drugs are working. If one or more seems clearly effective, they will switch all the subjects to it and continue the study, looking for clinical benefits.

The drugs to be tested are gantenerumab, made by Roche, which binds to clumps of amyloid and allows it to be removed from the brain, and two drugs by Lilly. One, known as LY2886721, blocks an enzyme, beta-secretase, used to make amyloid. The other, solanezumab, attaches itself to amyloid that is floating free in the brain before it clumps into plaques, facilitating its removal.

Solanezumab was recently tested in people with mild to moderate Alzheimer’s and appeared to have no effect on the disease. But Lilly also handed over all of its data to a group of academic researchers, giving them complete control of the presentation of their analysis and publication, and the group noticed something interesting. The investigators pooled data from the company’s two large clinical trials of the drugs. In their extensive analysis, presented Monday at the American Neurological Association meeting in Boston, they reported that it improved Alzheimer’s dementia, particularly in mild cases.

“This is the best news we’ve had in a decade,” said Dr. Paul Aisen, an Alzheimer’s researcher at the University of California, San Diego. Dr. Aisen helped analyze the Lilly data and is also a member of the DIAN TU committee that helped select the drugs for the clinical trial.

DIAN is hoping that the same sort of exquisitely sensitive cognitive tests will provide the first sign that one of the drugs is working.

If any of the drugs come to market, they will be expensive, which raises issues of how patients will ever be able to pay for them.

Researchers said they would face that issue when they come to it.

“Right now we have to get treatments that work,” said Dr. Rachelle S. Doody, director of the Alzheimer’s Disease and Memory Disorders Center at the Baylor College of Medicine. “Then we can put pressure on to bring down the cost.”

A version of this article appears in print on  , Section A, Page 19 of the New York edition with the headline: Three Drugs To Be Tested To Stave Off Alzheimer’s. Order Reprints | Today’s Paper | Subscribe

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