Drug Promising For Advanced Alzheimer's

March 27, 2002 -- An experimental treatment for Alzheimer's may allow treatment at a later stage than other medications, but some experts question the drug's benefits.

The drug, known as Memantine, has been on the market for a decade in Germany and was recently recommended for approval by the European Union's equivalent of the Food and Drug Administration.

Memantine works through a different mechanism than other, currently approved Alzheimer's drugs, such as Aricept, that have been shown to affect progression of early stage disease. The final devastating period, where Memantine may help, can also be the disease's most long lasting.

According to the Alzheimer's Association, four million Americans suffer from the disease, and there a currently no approved treatments for moderate to severe stages of the disease, when patients can start to lose the ability to care for themselves.

But researchers found that Alzheimer's patients who received Memantine deteriorated mentally at a considerably lower rate than patients who received placebo, according to results of a recent large nation-wide Memantine study presented last month at the meeting of the American Association for Geriatric Psychiatry in Orlando, Fla.

"Patients deteriorated one-half to one-third as far as they otherwise would have," says Dr. Barry Reisberg, principal investigator of the study and clinical director of the William and Silvia Silverstein Aging and Dementia Research Center at the New York University School of Medicine. Additionally, the drug was found to be safe and well tolerated.

Rethinking Expectations

While some are calling it a significant advance in the treatment of Alzheimer's disease, others remain much more cautious about the drug's potential and how it's benefits could be misinterpreted.

"It is safe to say that memantine brings no real 'quantum leap' in Alzheimer's treatment," says Dr. Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia, Pa. "These drugs are aimed at symptoms — at later changes — they are not aimed at the cause of the disease."

Others have also questioned why anyone would want to slow the rate of decline or maintain someone at an advanced stage of disease — seeing it only as a means of prolonging the inevitable.

Yet while experts say these benefits were small, they believe the slowed deterioration can have a big impact. People needn't expect a return to pre-disease functioning in order to accept a new drug.

"If you can hold [patients] off and keep them from getting worse for a long time, that's a huge benefit," says Dr. Rachelle Doody, Effie Marie Cain Professor in Alzheimer's Disease Research at the Alzheimer's Disease Center at Baylor College of Medicine in Houston, Texas, who also participated in the Memantine trial. "You can have some really important preservation of functions even in people who are severe."

Slowing the rate of decline at advanced stages can mean that someone may retain the ability to dress or bathe themselves or retain continence for longer periods of time. These gains can improve quality of life for the patient as well as the caregiver.

"Only about 20 percent of our patients in our Alzheimer's disease center ever go into a nursing home" adds Doody. "The majority of people live out their life at home."

Therefore, drugs like Memantine may make life easier for the majority of caregivers who look after loved ones with the disease at home and may not have the resources that would be available in a nursing home.

Experimental Potential

Forrest Pharmaceuticals, the U.S. manufacturer of the drug, is expected to file for FDA approval sometime this year. The company is also exploring uses for the drug in earlier stages of the disease and in conjunction with currently approved treatments.

And despite cautions against misinterpreting the potential clinical benefits of Memantine, experts are enthusiastic about what the study results mean for laboratory science and how they translate into human treatments.

"The excitement here comes from having confirmed that it is possible to use our basic science research on mice and isolated nerve cells to successfully alter the course of Alzheimer's in a human suffering from the disease," says Gandy. "This positive feedback suggests that much of what we think we know about the disease might actually be true."

That means that even if Memantine itself does not continue to show benefit in future studies, its development may pave the way for other similar treatments and increase enthusiasm for attaining a better understanding of Alzheimer's disease mechanisms.

"Such information about the causes and very earliest brain abnormalities will soon lead to the discovery of drugs that might well be effective at preventing, treating, or perhaps even reversing the devastation that Alzheimer's wreaks on the brain," explains Gandy.