An interim analysis of cognitive tests of 27 patients reaching Study Week 88 showed statistically significant, dose-dependent improvements in participants' cognitive abilities. Study participants who carried one or two copies of the ApoE4 gene, which increases the risk of Alzheimer's, performed significantly better than ApoE4 non-carriers on two of the cognitive tests.
"This is one of the first studies indicating that this neuroinflammatory inhibitor may be able to improve cognition in people with MCI who carry the ApoE4 gene," said Ross. " CHF5074 was well tolerated by people with MCI at doses up to and including 400 mg/day."
MK-8931 (BACE1 Inhibitor) Lowers Beta Amyloid in People with Mild to Moderate Alzheimer's
The presence of beta-amyloid plaques in the brain is a well-known manifestation of Alzheimer's disease. One hypothesis holds that the toxins produced by beta-amyloid initiate a cascade of events in the brain that cause Alzheimer's, but it is still unclear to many whether the plaques are a cause or a result of the disease.Academic and industry researchers have investigated a variety of approaches to slow or stop the production of beta-amyloid and/or clear it from the brain. Yet, to date, some combination of safety concerns and lack of efficacy in slowing or stopping cognitive decline in people with Alzheimer's has plagued all of these attempts. While this has led to further questions about the validity of the amyloid cascade hypothesis, or the possibility of therapeutic intervention through this route, new approaches continue to be tested. Mark S. Forman, M.D., Ph.D., and colleagues at Merck Research Laboratories conducted a randomized, double-blind, placebo-controlled, multiple-dose study of an experimental medication called MK-8931 in people with mild-to-moderate Alzheimer's. The drug acts by inhibition of beta-secretase (BACE1), one of two enzymes that produce beta-amyloid by breaking down its parent molecule, known as amyloid precursor protein (APP). Participants received 12, 40 or 60 mg of MK-8931 or placebo (n=8 per dose; n=6 for placebo) daily for seven days. Beta-amyloid levels were measured in cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord) obtained by lumbar puncture over 36 hours following the final dose. The researchers found that the drug significantly lowered CSF beta amyloid in people with mild to moderate Alzheimer's in a dose-dependent fashion; at the highest dose, the average reduction from baseline was more than 80 percent. According to the researchers, MK-8931 was generally well-tolerated.