Drugs may be sold to prevent Alzheimer's
News Analysis () —
c.2010 New York Times News Service@
Will Alzheimer's disease, a terrible degenerative brain disease with no treatments and no clear guidelines for diagnosis before its end stages, become like heart disease? That might mean early markers of risk, analogous to high cholesterol levels, that predict who is likely to get it. And it might mean drugs that actually prevent it.
That is the hope behind new diagnostic guidelines being proposed by the National Institute on Aging and the Alzheimer's Association.
In July, when the groups first announced their proposed guidelines, they were met with some skepticism and anger. Why suggest ways of diagnosing the disease before a person even has symptoms? Why tell people they are doomed?
And are those early diagnosis guidelines just a sop to pharmaceutical companies so they can start marketing expensive, and perhaps not very effective, new drugs?
So the Alzheimer's Association, with participation from the National Institute on Aging, held a conference call on Wednesday to clarify their position.
They wanted, in particular, to explain why they advocated using so-called biomarkers, like scans for amyloid plaque in the brain, a unique feature of Alzheimer's, and tests of cerebrospinal fluid. Such brain scans are still experimental.
The groups said biomarkers would be used, at this stage, only for research, with some patients in studies having tests to see how well such brain changes predict disease.
A main goal of the proposed guidelines, which are expected to be adopted, is to find signs of the disease much earlier. Now, the diagnosis — based on declining memory and reasoning abilities — requires severe symptoms. But researchers agree that Alzheimer's smolders in the brain a decade or more before memory loss or diminished ability to reason. With new criteria for early diagnosis, the stage is set for testing drugs that might prevent the disease from running its course, investigators say.
''Certainly, we are not out there trying to help drug companies," said Dr. Reisa Sperling of Brigham and Women's Hospital in Boston. But the situation today — nearly all drugs are tested only in people who have severe symptoms — seems a recipe for failure.
''We are trying these drugs way too late," Sperling said in a telephone interview on Tuesday.
But, said Dr. Jason Karlawish, an Alzheimer's researcher at the University of Pennsylvania who was not part of the conference call, it is not unreasonable to worry about the role of drug companies.
''They are driven by profits over progress and by trying to move a drug as fast as they can into the clinic without getting all the good evidence they need," Karlawish said.
The challenge, he said, is to avoid a rush to approve drugs that are not truly effective and to find a way to keep prices reasonable.
And there is a challenge in making sure diagnostic tests are not misused.
That may not be easy.
Already, some doctors are using biomarkers, like spinal fluid tests that are commercially available, against the advice of researchers. Scientists are still working on standardizing the tests — making sure that, like a test for cholesterol or prostate cancer, an Alzheimer's biomarker test done in one lab will give the same results as one done elsewhere. The spinal fluid tests can show levels of amyloid and another Alzheimer's protein, tau. But it is not yet known what levels of amyloid or tau in spinal fluid are abnormal. And measurements of amyloid and tau can vary as much as 30 percent from one research lab to another, said Dr. Marilyn Albert of Johns Hopkins University. "That's why we are very concerned about these measurements being used in clinical settings at the current time."
The investigators said people worried about their memory should consider entering clinical trials studying the natural history of the disease and testing new drugs. It might be a decade or more before any drugs are found to work and approved for marketing. So there is not much people can do if they go to a private doctor, have a spinal fluid test and are told they might be in the early stages of Alzheimer's. The test might not be valid, and no drugs now on the market can slow the disease.
The biggest questions are what it means when tests find that people have amyloid in their brain yet have no symptoms. Are those people certain to develop Alzheimer's if they live long enough? Or is brain plaque like the very different plaque that forms in arteries? Many people have plaque in their arteries yet never have a heart attack.
If amyloid plaque is analogous to artery plaque, some who take drugs would be protected from Alzheimer's. But many others who would never get Alzheimer's might end up taking drugs for decades. That means the drugs must be very safe and not prohibitively expensive.
Even so, said Dr. Steven DeKosky, the dean of the University of Virginia medical school, the future now looks brighter than it ever has.
He and others are convinced the field is at a turning point, resembling the early days of cholesterol testing for heart disease.
''This is where we're going in Alzheimer's disease," DeKosky said.