Alzheimer’s disease has no cure, but two new drugs recently approved by the US Food & Drug Administration (FDA) may help make the symptoms more bearable. A new study from the University of Colorado Anschutz Medical Campus finds that the antidepressant imipramine and antipsychotic olanzapine inhibit amyloid-beta plaques, which worsen the progression of Alzheimer’s.
“The people who received these drugs developed better cognition and actually improved in their clinical diagnosis,” says senior author Huntington Potter, PhD, a professor of neurology and director of the CU Alzheimer’s and Cognition Center, in a statement. “Compared to those who did not take these drugs, they reverted from Alzheimer’s disease to mild cognitive impairment or from mild cognitive impairment to normal.”
Both drugs are considered safe and effective for depression and psychosis. Since these two psychiatric conditions are somewhat associated with Alzheimer’s, it would not be unusual for this patient population to take these drugs.
The team originally searched for drugs that could block the effect of the apolipoprotein E4 protein or APOE4. Some people with Alzheimer’s disease have a genetic mutation for APOE4, which increases their risk of developing the disease. “We took a unique approach by targeting APOE4 because the usual drug targets, amyloid-beta and tau, have not produced a convincingly effective drug for people with AD despite decades of work,” says senior author Noah Johnson, PhD.
They screened 595 compounds in a drug library compiled from the National Institutes of Health. In their search, they found multiple compounds that could have the power to block APOE4, and therefore block amyloid plaques that create clumps in the brain and stop cells from carrying out their duties. Two drugs with these compounds included imipramine and olanzapine.
When the team observed the symptoms of people with Alzheimer’s disease who also took either drug, they found better improvement in their cognition compared to people with Alzheimer’s not on these drugs. “The only things these drugs have in common is that they block the catalytic effect of APOE4 on the formation of amyloids in the brain,” explains Dr. Potter.
The next step is to test the effectiveness of the drugs. A mouse model of Alzheimer’s will help to test how well the drug works and any concerning side effects. If successful, they may test the drugs in a human clinical trial.
“The number of human drugs that have shown any benefit to AD patients are maybe one or two or three,” says Dr. Potter. “So this is a very promising advance.”
The study is published in the journal Alzheimer’s Research & Therapy.