New Merck Drug May Be the Cure for Alzheimer's Disease

Alzheimer's disease may be yesterday's news -- if a project by Merck becomes successful in its clinical trials.

A team from Merck Research Laboratories has reported the results of early human and animal trials of a drug called verubecestat. In their study published in Science Translational Medicine, the drug targets the production of protein plaques associated with Alzheimer's.

Team leader Matthew Kennedy said the study details the early discovery and profiling of verubecestat. The team is hopeful it could one day be a therapeutic treatment for the  neurocognitive disorder.

According to Science Translational Magazine, verubecestat functions as a BACE1 inhibitor. BACE1 (beta-site amyloid precursor protein cleaving enzyme 1, or the beta-secretase 1) is involved in producing a protein called amyloid beta that forms the plaques associated with the disease.

Scientists hypothesize that the accumulation of amyloid beta in the brain leads to neurodegeneration. Experts hope that by blocking BACE1, the build-up of amyloid beta can be avoided.  

However, the drug is still undergoing phase 3 of its clinical trial. If the results are positive, this means the drug may finally be used on patients.

Amyloid is formed when amyloid precursor protein (APP) is sliced up by BACE1 and another protein called gamma-secretase. APP can be found in cell membranes and goes to spaces in between cells to be cut.

BACE1 inhibitors function by attaching itself to enzymes and prevents BACE1 from cutting APP. They were discovered by 1999, and researchers have been studying them ever since.

However, studies with mice lacking the BACE1 gene revealed numerous side effects, such as problems with insulation and guidance of neural wiring, retinal pathology, and neurodegredation.

Not only that, it will also be difficult to develop molecules big enough to attach BACE1 but small enough to cross the blood-brain barrier.

However, a team from Merck was able to develop such a molecule, and recent tests on animals have significantly lessened amyloid levels in the blood. Furthermore, the study showed no signs of toxicity in treatments of animals up to six months.

When they proceeded to small and early-stage human trials, verubecestat reduced amyloid in the cerebrospinal fluid of healthy adults that underwent treatment for weeks and patients with mild to moderate Alzheimer's disease who took it for a week.

The good news is that the participants did not exhibit any side effects at all. Merck said this may be due to the fact that BACE activity is still needed in the brain to avoid side effects.

According to Scientific American, this made verubecestat the first BACE1 inhibitor to actually reach Phase III of human trials. Their current tests involve 2,000 patients with mild to moderate Alzheimer's to undergo treatment for 18 months. The next one will involve 1,500 participants with early signs of Alzheimer's for two years.

The latter is the more crucial test, given that the best way for drugs like verubecestat to work is to inhibit Alzheimer's in its early stages.