WALTER Skotchdopole worked for 20 years as a police officer and 20 years in the film industry before succumbing to the relentless decline of Alzheimer’s disease. In his prime, he joked with everyone he met. By his early 70s, he had become a shell of his former self.
“He’s there, but he’s not,” says his son James Skotchdopole. “There’s no real interaction, no real stake in life.”
Walter Skotchdopole had tried several drugs, with no noticeable improvement. But when he began experimental treatments with Enbrel (etanercept) — a drug commonly used to treat rheumatoid arthritis — it was as if someone flipped a switch.
Within minutes of his first injection, he was making jokes. Later that afternoon, he ditched his cane to dance with a worker at his assisted-living facility. After a year and a half of weekly injections, Skotchdopole still gets confused sometimes, but requires far less help than he used to.
“The results we’ve seen are unprecedented with any kind of treatment,” says Dr. Edward Tobinick, an assistant clinical professor of medicine at UCLA who led a recent pilot study of Enbrel’s effects on 15 Alzheimer’s patients.
Though still preliminary, the study’s findings add to a growing list of approaches that scientists are taking to uncover the biological roots of Alzheimer’s and hit the disease where it hurts.
About 4.5 million Americans have Alzheimer’s disease, and healthcare costs total $100 billion a year, according to estimates by the Alzheimer’s Assn. and the National Institute on Aging. By 2050, there could be as many as 16 million people with the disease.
Since 1992, the Food and Drug Administration has approved five drugs for treating the forgetfulness, communication problems and other traits of Alzheimer’s. All of them target one of two key brain chemicals that help brain cells communicate and facilitate learning and memory. But the drugs — Aricept (donepezil), Razadyne (galantamine), Exelon (rivastigmine) and the newest, Namenda (memantine) — treat only symptoms, not the underlying disease. They just slow the rate of decline, and only for a year or two.
Researchers think they can do better by focusing on the root causes of Alzheimer’s.
Most research targets the accumulation of a sticky protein called amyloid in the brains of Alzheimer’s patients. The protein forms clumps, called plaques, that damage brain tissue. Various research groups are developing drugs that might reduce this buildup, keep the amyloid from clumping together or get rid of plaques after they’ve have formed.
Trials of a vaccine designed to clear the brain of amyloid were halted by Elan Pharmaceuticals in 2002, because 18 of 300 participants developed serious brain inflammation. But scientists continue to work on more selective vaccines that could help the body fight amyloid without harming surrounding tissue, says Dr. John C. Morris, director of the Alzheimer’s Disease Research Center at Washington University in St. Louis.
Tobinick and colleagues have focused on the inflammation that happens in the brain as a result of both amyloid buildup and the accumulation of another protein, called tau, which forms “tangles” that damage brain cells. The researchers chose to investigate Enbrel because it disables an inflammation-promoting molecule called tumor necrosis factor-alpha. TNF-alpha causes joint pain in people with autoimmune diseases such as rheumatoid arthritis. In Alzheimer’s, it sparks the immune system to attack brain tissue.
When used to treat patients with arthritis, Enbrel is injected into the arms or abdomen. That doesn’t work with Alzheimer’s patients. Studies show that TNF-alpha is as much as 25 times more abundant than normal in the spinal fluid of people with Alzheimer’s. So, with a tiny needle, Tobinick injects the drug into the back of the neck, above the spine, which is thought to improve delivery to the brain.
The procedure is simple, he says, and the preliminary results, published in April, have been both quick and long lasting. “Memory improves. People have a better grasp of language. They can do things they couldn’t do before.”
Attacking inflammation makes sense, says Sue Griffin, director of research at the Geriatric Research Education Clinical Center at the University of Arkansas, in Little Rock. “There is really good evidence,” she says, “that quelling neuroinflammation is a very good thing for Alzheimer’s disease.” A population study published last year in the Journal of Geriatric Psychology and Neurology found that people who’d used anti-inflammatory drugs daily for more than two years had a 25% lower risk of developing Alzheimer’s.
Still, many researchers remain cautious. The Enbrel study was extremely small. It lacked controls — people taking a placebo to compare with patients who got the real drug. And it has not yet been replicated by other scientists.
Tobinick, who owns a patent for his treatment method as well as stock in Amgen, the company that produces Enbrel, says he is eager for other scientists to replicate his results.
James Skotchdopole, meanwhile, remains hopeful that his father will enjoy a longer life, that his 10-year-old daughter will get a chance to really know her grandfather, and is more optimistic about his own future. “I’m 42, and I see 75 as not that far away,” he says. “I’m excited that there is progress. I felt my future was a fait accompli.”
Source: Los Angeles Times (19 Jun 2006)