New Alzheimer’s research impacting female mice could help steer future drug trials

Innovative new research at the uOttawa Faculty of Medicine could serve as a guidepost for steering future drug trials aimed at reversing memory deficits and easing the onset of Alzheimer’s disease, a devastating neurological illness that’s the most common form of dementia across the globe.

The findings from Dr. Stephen Ferguson’s lab, published online this week in the British Journal of Pharmacology, demonstrate how a novel drug exhibiting minimal side effects is effective at battling memory loss and reducing the production of toxic deposits in the brains of female mouse models of Alzheimer’s disease. These deposits can also be found in the human brain and are considered a pathological hallmark of Alzheimer’s.

It’s the first paper to demonstrate the therapeutic potential of activating the well-studied M1-muscarinic receptor in the brains of female Alzheimer’s mice with a highly targeted approach. That’s potentially impactful as Alzheimer’s disproportionately impacts women, who make up roughly two-thirds of diagnosed cases.

“We found that activating this particular receptor was very effective in reversing memory deficits in female mice along with slowing the progression of the disease,” says research associate Dr. Khaled Abdelrahman, who led the study alongside Dr. Ferguson. Both researchers work out of the Faculty of Medicine’s Department of Cellular and Molecular Medicine and the uOttawa Brain and Mind Research Institute.

Thse findings could contribute to an evolving framework on how to treat individuals afflicted with Alzheimer’s, which begins with mild memory loss and can lead to a heartbreaking inability to remember loved ones or even hold a basic conversation.

The prevalence of the harrowing disease is only accelerating with the aging of the global population. More than 55 million people worldwide live with dementia, and Alzheimer’s may be contributing to 70 percent of cases, according to the World Health Organization.

The uOttawa researchers’ latest findings follow their breakthrough last year demonstrating that one sex-specific Alzheimer’s treatment may benefit males over females, providing a window into the effectiveness of targeted treatments. For that study, they utilized post-mortem brain tissue from male and female human donors to corroborate findings.

Dr. Ferguson was initially surprised that the findings pointed to fundamental differences with how specific targeted treatments interact with receptors in male and female brains. He says the latest work with female mice perhaps lends credence to the possibility that there may be sex-tailored therapies for Alzheimer’s in the future.

One of the most chilling aspects of Alzheimer’s, according to Dr. Abdelrahman, is the scar­city of effective treatments. Those available now only treat symptoms. Recently, there has been some promising movement on the therapeutic front for Alzheimer’s treatment after decades of frustration, and Dr. Abdelrahman is hopeful that his research contributions can one day help to halt the progression of the scourge.

“I think there are many drugs that will slow the disease’s progression in coming years,” he says. “And I think the drug that we tested in this study is one that will be very promising down the road.”