A new drug aimed at treating Alzheimer's disease (AD) may have deleterious side effects, according to the scientist who discovered the compound's molecular target. Northwestern University cell and molecular biologist Robert Vassar warns that a drug designed to inhibit BACE1, an enzyme that aids in the development of the amyloid plaques that are characteristic of AD, may also stop the enzyme from performing a crucial neuron-mapping function in the brain. Vassar's group cloned and characterized BACE1 in 1999.
Vassar recently showed that mice devoid of BACE1 had olfactory neurons that were improperly wired to the olfactory bulb. This is worrying, Vassar said, because in the hippocampus, as memories are formed, neurons are continually reborn and connections reconfigured, making BACE1's organization role hugely important. Thus, drugs like the BACE1 blocker that is now in clinical trials could impair memory.
"Let's proceed with caution," he said Saturday at the annual meeting for the American Association for the Advancement of Science. "We have to keep our eyes open for potential side effects of these drugs."
"It's not all bad news," Vassar added. "These BACE1 blockers might be useful at a specific dose that will reduce the amyloid plaques but not high enough to interfere with the wiring. Understanding the normal function of BACE1 may help us avoid potential drug side effects.
Vassar is publishing the results of the recent mouse study that points to the potential problem with inhibiting BACE1 in the journal Molecular Neurodegeneration.