Alzheimer's disease is one of the modern world's greatest scourges. Not only does it rob 4 million aging Americans of their minds every year but it costs the country more than $100 billion annually in medical expenses. And unless effective treatments are developed, the problem will only get worse -- much worse. About 1 in every 10 people over the age of 65 has the disease. As America's population ages, the number of victims is expected to soar to 14 million by 2050.
Now, a small clinical trial of a new drug offers hope that it may be possible to prevent the disease's terrible dementia. Predicts Francesco Bellini, chairman and CEO of Montreal biotech outfit Neurochem: "We're on the verge of a major breakthrough in Alzheimer's. This is going to stop the disease." (Neurochem is listed on the Toronto Stock Exchange under the ticker symbol "NRM".)
TANTALIZING POTENTIAL. Bellini's optimism is more than a bit premature. The trial involved only 58 patients. Years of additional testing will be needed before the Food & Drug Administration can certify the drug as safe and effective. And other Alzheimer's drugs hailed as potential breakthroughs have failed to live up to their promise. This one, too, may stumble farther down the long road to market. But the results Neurochem announced on June 23 at the Biotechnology Industry Organization's annual meeting in Washington, D.C., are at least encouraging.
All the recruited patients suffered from mild to moderate Alzheimer's disease. Half received Neurochem's new drug, Alzhemed, along with a currently available drug, Aricep, which offers Alzheimer's patients only a small, temporary boost in mental function. The other half -- the control group -- only got Aricep.
Six months later, in keeping with Alzheimer's usual tragic pattern, the cognitive abilities of those in the control group had declined. But those taking Alzhemed didn't get any worse. They even performed slightly better on the mental exercises. In addition, biochemical analyses show that those taking Alzhemed have lower levels of the toxic protein that helps cause the disease in the first place.
KILLER PLAQUE. To understand how Alzhemed works, start by considering how the disease develops. Back in 1906, when German physician Dr. Alois Alzheimer examined the brains of people who had died after a long slide into severe dementia, he noticed numerous clumps of tangled material. Since then, scientists have learned that these clumps, called plaques, are made up of fragments of a protein called amyloid. (Neurochem is also testing a number of other amyloid-related treatments, including experimental medications for stroke, diabetes, and epileptic seizures.)
Why the amyloid plaques occur at all is still a big mystery, but scientists are beginning to understand the biological mechanism to leads to Alzheimer's disease. Normally, dissolved amyloid floats in the bloodstream, like sugar in coffee. In people who develop Alzheimer's disease, amyloid binds to other substances, called glycosaminoglycans, or GAGs. This union causes the protein to precipitate out of solution and form those solid clumps in victims' brain. Eventually, or so it seems, the plaques kill brain cells and prompt Alzheimer's characteristic mental decline.
So what would happen if the amyloid protein could be kept from precipitating into clumps? Neurochem scientists sought an answer by developing drugs that attach to the protein and prevent amyloid from binding to the GAGS, thus keeping the protein in the blood, where it remains harmless. Some evidence even shows that the amyloid in solution is then eliminated by the body, so less of it is floating around to cause trouble.
PREVENTION, NOT CURE. Alzhemed can't reverse the damage caused by already-existing plaques, meaning that the medication offers no hope of a cure to those who already have Alzheimer's. But if it really can stop the disease process -- something that remains to be proven -- it offers the hope that the illness' inexorable decline can be stopped in its tracks. Bellini even suggests that, eventually, the drug might be used to prevent the disease from starting at all. At the very least, it might be administered early enough to prevent further mental deterioration.
So far, the side-effects have been mild -- a bit of vomiting when first administered to some patients. A large Phase III trial, expected to begin early next year, will help scientists and regulators learn if other side effects may occur -- or if the drug works as well as these first results suggest.
Meanwhile, even more ambitious plans are afoot to tackle the disease. One idea is to harness the body's own immune system to fight the amyloid plaques. If you inject the amyloid protein into the body, like a vaccine, it can stimulate the immune system to produce antibodies. In theory, the antibodies attack the plaques and remove them from the brain. The approach works spectacularly well -- in mice. But when an Ireland-based outfit, Elan, tried it in people, a dangerous side effect appeared: The vaccination caused such serious brain inflammation that the trial had to be halted.
TARGETED ATTACK. A way around this problem may exist, however. Neurochem scientists believe that the inflammation occurred because the amyloid "vaccine" induced the formation of too many kinds of antibodies. Some attacked the plaque, just as researchers hoped. But others hit different targets, causing the side effects. The key, therefore, is creating a vaccine that stimulates antibodies against the plaque alone. Neurochem scientists believe they can accomplish this by using just a part of the amyloid protein as a vaccine. It works in mice but hasn't yet been tried in people.
All of this work is preliminary, of course. Neurochem's promising Phase II results don't mean that the problem of Alzheimer's has been solved. But for the first time since Dr. Alois Alzheimer spotted this devastating ailment, there's a glimmer of hope that it might eventually be tamed. By John Carey in Washington