Desperate to stop Alzheimer's in its tracks, some caregivers are clamoring for a cancer drug shown to reverse the disease in mice. But experts argue prescribing the drug, while legal, is unethical.
"[E]ven if patients and families are willing to take the risks for the potential benefit, the physician's answer should be no," Justin Lowenthal and colleagues from the National Institutes of Health and Massachusetts General Hospital wrote in an editorial published Wednesday in the New England Journal of Medicine.
The editorial was prompted by a February 2012 study published in the journal Science, that found the drug, bexarotene, relieved Alzheimer-like symptoms in three mouse models of Alzheimer's disease. The drug has yet to be tested in human patients. But because it's approved by the U.S. Food and Drug Administration for a form of skin cancer, doctors can choose to prescribe it off-label.
"Off-label use of medications without proper testing may expose patients and their families to serious side effects without the possibility of benefit," said Dr. James Galvin, an Alzheimer's specialist at NYU. "In the absence of any human trials, I do believe it unethical to prescribe a medication without evidence of efficacy and safety."
Like other cancer drugs, bexarotene can produce serious side effects, including headaches, hair loss, nausea and depression, and can increase cholesterol levels, according to the National Institutes of Health. In elderly Alzheimer's patients, many of whom take multiple medications, bexarotene could interact and interfere with other drugs.
Most current medications used in Alzheimer's disease are aimed at symptom relief, addressing problems such as depression, hallucinations, agitation and nutrition. But bexarotene is thought to attack the disease directly by cleaning up beta-amyloid protein plaques in the brain. While other treatments targeting beta-amyloid have shown promise in mouse models, they've been largely unsuccessful in humans.
"No mouse data should ever get this kind of ill-advised attention because of a track record of failures," said Dr. Peter Whitehouse, a neurologist at University Hospitals Case Medical Center in Cleveland.
But for the 5.4 million Americans with Alzheimer's disease and their 10 million caregivers, waiting for human clinical trials is a tall order. And some doctors say patients and caregivers who understand the risks of an experimental drug should be allowed access.
"If the physician and patient are both suitably well-informed ... an argument could be made that it would be unethical to withhold treatment from a patient who requests it just because the definitive clinical trial had not yet occurred," said Dr. Clifford Saper of Harvard Medical School.
The dearth of effective Alzheimer's drugs has prompted some families to travel abroad for risky, unproven therapies.
"If the patient and family members are fully aware of the risks and in their desperate efforts they are contemplating bexarotene treatment or going to Mexico to be treated with even more questionable and riskier stem cell treatments being surgically introduced into their brains, then they should have the opportunity for the relatively safer bexarotene option," said Dr. George Bartzokis, professor of psychiatry at the University of California, Los Angeles.
Clinical trials for promising treatments continue, and Dean Hartley from the Alzheimer's Association is optimistic about one day finding a treatment for Alzheimer's disease.
"I think we will find one," he said. "It's just a matter of when."