A promising approach in mice disappoints in human trial
WEDNESDAY, Nov. 19 (HealthDay News) -- A compound that boosts growth hormone levels in Alzheimer's patients may not slow the disease, new research suggests.
The study, funded by drug giant Merck, was spurred by promising animal research that had suggested that the compound, called MK-677, might help curb Alzheimer's effect on the brain.
However, "the study suggests that targeting this hormone system may not be an effective approach at slowing the rate of Alzheimer's disease progression," said study author Dr. J.J. Sevigny, associate director of clinical neuroscience at Merck Research Laboratories in North Wales, Pa. His team reported its finding in the Nov. 18 issue of Neurology.
"In a similar vein, the study challenges a commonly held theory that hormones may attack beta-amyloid plaque in the brain," Sevigny added. "That was the premise of this research: that by giving this medication we'd be able to influence the beta-amyloid in the brain. And we didn't receive this result in this study."
Based on the findings, Merck has now stopped investigating MK-677 for use against Alzheimer's.
The study comes on the heels of another report on the drug, published earlier this month in the Annals of Internal Medicine.
In that study, researchers at the University of Virginia found the use of MK-677 spurred an increase in muscle mass in older recipients. It also improved their fat distribution and boosted appetite as it restored the body's production of growth hormone to youthful levels. The intervention did not demonstrate any specific benefit with respect to boosting overall muscle strength or activity function, however.
In the new study, conducted between 2003 and 2005, Sevigny's team tracked the cognitive health of 416 U.S. patients with mild to moderate Alzheimer's disease, aged 50 and above.
During the study, half the patients received 25-milligram tablets of MK-677, while the other half consumed a placebo.
The researchers found that MK-677 was well-tolerated and produced a desirable 60 percent-plus increase in the pituitary gland's production of insulin-like growth factor-1 (IGF-1) within just six weeks. This boost increased to nearly 73 percent by the end of one year.
Prior work with mice has suggested that a rise in IGF-1 might trigger a drop in levels of beta-amyloid brain plaque, long associated with Alzheimer's disease. So the hope was that plaques -- and associated symptoms -- might decline in Alzheimer's patients as IGF-1 levels rose.
However, after rating patient mental health according to a standard "clinical dementia" scale the authors found that the MK-677-mediated boost in IGF-1 did not translate into any slowdown in Alzheimer's disease progression.
Although the study has offered meaningful opportunities to learn a "tremendous amount about the possible causes of Alzheimer's disease", Sevigny said his team at Merck will now be "moving on to other options" for therapeutic research.
Maria C. Caprillo is director of medical and scientific relations at the national office of the Alzheimer's Association in Chicago. She said that growth hormone therapy's failure to stem disease progression might be due to the fact that plaque build-up can begin as much as 10 years before an Alzheimer's diagnosis.
"So, even though animal work has suggested that growth hormone could be neuroprotective, it's not too surprising that it didn't have an effect, given that when you're looking at mild-to-moderate Alzheimer patients it simply may be a little too late," she said.
"Regardless of the reason -- and there are still a lot of unknowns -- the bottom line is that this compound did not produce positive results, and did not improve cognition or the ability to carry out the activities of daily living," Caprillo noted. "Which is, of course, disappointing -- that another line of potential research may not prove fruitful for people who so desperately need something today."
For more on the role of plaque in Alzheimer's, visit the Alzheimer's Association.
SOURCES: J.J. (Jeffrey) Sevigny, M.D, associate director, clinical neuro-science, Merck Research Laboratories, North Wales, Pa.; Maria C. Carillo, Ph.D., director, medical & scientific relations, Alzheimer's Association, National Office, Chicago; Nov. 18, 2008, Neurology
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