Drug fails in one BU Alzheimer study, hormone link seen in other

By Elizabeth Cooney, Globe Correspondent

Two new studies from Boston University shed light on the complexity of Alzheimer's disease, one ruling out a drug that looked promising in the lab and another showing an association between  an appetite-controlling hormone and a lower risk of developing the disease.

Dr. Robert Green, a professor of neurology, genetics, and epidemiology at BU's School of Medicine, led a large, randomized clinical trial of tarenflurbil, a drug  that targets an enzyme important in producing amyloid beta protein. Excessive accumulation of amyloid tangles in the brain is believed to cause the symptoms of Alzheimer's. The drug, made by Myriad Pharmaceuticals, had previously shown some effectiveness in the test tube and lab animals. In a trial of the drug in people, there was a suggestion that patients with mild disease might benefit. 

Based on these preliminary results, more than 1,600 patients with mild Alzheimer's disease at 133 sites were divided into two groups. After 18 months, the group taking tarenflurbil had the same rates of cognitive and functional decline as the group taking a placebo. 

"The drug did not work," Green said in an interview about the trial, which Myriad paid for. "There are people who are wondering if we were right about the amyloid hypothesis, but I think it's too early to say on the basis of one trial. This is just one compound and just one trial."

Rudolph Tanzi, a professor of neurology at Harvard Medical School and a geneticist at Massachusetts General Hospital, was not surprised that tarenflurbil was ineffective, calling it a weak member of the class of compounds designed to lower amyloid levels. He is involved in two companies developing other modulators. "The failure of this drug in no way challenges the amyloid hypothesis for drug discovery."

In the other BU study appearing in tomorrow's Journal of the American Medical Association, Dr. Sudha Seshadri reports on an association between leptin and risk for Alzheimer's disease. Leptin is active not only in the part of the brain that controls appetite, but also in another brain region involved in specific memories, such as where you parked your car.

She and her colleagues studied 785 original participants in the Framingham Heart Study with an average age of 79 who did not yet have dementia. People who had leptin levels in the top 25 percent had a 6 percent risk of developing Alzheimer's disease over the next 12 years. People who had leptin levels in the lowest 25 percent had a 25 percent risk of developing Alzheimer's over the same time period.

"We are not suggesting for a minute that leptin is going to be the only or even the major pathway in Alzheimer's pathogenesis, ... but it could be one more," Seshadri, a professor of neurology at BU, said in an interview.

Tanzi said the most interesting thing about the study is the possible link leptin might represent between appetite and obesity, which could be risk factors for Alzheimer's disease. "To use leptin as a biomarker for Alzheimer's disease based on levels in the blood is an interesting prospect, but certainly we would need to see further confirmation and extension of these findings."