In a study from Indiana University School of Medicine and elsewhere, scientists found an anti-seizure drug used to treat epilepsy in children and adults could be repurposed as a potential therapeutic for Alzheimer’s disease.
In the study, the team first performed experiments to determine the optimal dose strategy and range in a mouse model that overlaps with some aspects of human Alzheimer’s disease.
They followed this with a chronic dosing study using multiple doses of the drug.
The researchers focused on what could translate directly to the human clinic, including PET/MRI scans using a tracer to assess bran amyloid deposition and a tracer to assess brain activity.
Sequencing of brain tissue was also performed to look at gene expression changes that occurred as the result of drug treatment.
The team chose to test the anti-seizure medication because of its current clinical trial status.
They also highlighted that it was important to select a drug that had a non-traditional mechanism of action, outside of the typically used amyloid-lowering compounds.
As Alzheimer’s disease can cause hyperexcitability in neurons in the brain, the hope is that the use of an anti-epileptic will help bring the brain back to normal levels of functioning.
Levetiracetam binds to a specific receptor in the brain, SV2A, which is still being investigated regarding its overall function. Blockade of this receptor appears to lower overall levels of neurotransmitter release.
The researchers say that dialing back neurotransmitter release would lead to reduced hyperexcitability in the brain.
Based on their work, the team discovered important sex differences in the effects of levetiracetam. Overall, the disease state showed the greatest improvement in female rather than male mice.
While this could be for several reasons, it’s promising as women are more likely to be afflicted with Alzheimer’s disease, independent from increased longevity.
The team provides their findings as a resource to the broader research community, and researchers can visit stopadportal.synapse.org to submit compounds for consideration.
If you care about brain health, please read studies about how unhealthy blood pressure increases your dementia risk, and sleep loss in middle age may increase dementia risk.
For more information about brain health, please see recent studies that cranberries could help boost memory, and these antioxidants could help reduce dementia risk.
The study was conducted by Paul Territo et al and published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
Copyright © 2022 Knowridge Science Report. All rights reserved.
