Using existing medication as a blueprint for a cure
Praveen Nekkar
Professor, Faculty of Science
> University of Waterloo
> School of Pharmacy
A new breakthrough is offering hope to people living with Alzheimer’s disease and their families.
Praveen Nekkar, a professor at the University of Waterloo School of Pharmacy, has discovered that two common medications for depression and mood disorders — fluoxetine and paroxetine — have the potential to slow the advancement of Alzheimer’s disease and dementia.
The finding, published in the journal ACS Chemical Neuroscience, is significant because it could be the key to preventing and ultimately curing the disease. It could not come at a more critical time, as the numbers of those living with Alzheimer’s disease reach epidemic proportions.
One of the main causes of Alzheimer’s disease is the clumping of amyloid-beta proteins to form plaques in the brain, inhibiting communication between nerve cells. Nekkar’s lab discovered that selective serotonin uptake inhibitors (SSRIs), which are currently used as antidepressant medications, prevent the binding of these proteins. Administered early enough, these medications can delay the onset of the disease by two to three years.
“We’re looking at the chemical structures of SSRIs as a blueprint to help inform future drug development,” Nekkar explains. “The goal is to create a molecule that will both prevent and cure the disease.”
The above image shows how a SSRIs bind to a string of amyloid beta. By taking up this binding spot, the SSRI prevents the proteins from clumping together to form plaques in the brain.
As one of the early researchers at the School of Pharmacy, Nekkar leads a team of graduate students and co-op undergraduate students who provide a combination of expertise in analyzing Alzheimer’s disease.
For Nekkar, finding a cure is personal. Alzheimer’s and dementia have affected members of his family. He’s seen first-hand how this devastating disease robs people of their independence and causes emotional and financial distress.
Approximately 20 to 40 per cent of those afflicted with Alzheimer’s also suffer from depression. In fact, depression can be an early indicator of the potential development of Alzheimer’s. As the research team investigated the link between depression and dementia further, it was evident that a similar accumulation of amyloid-beta proteins occurs in clinically depressed subjects.
It’s this connection that gave Nekkar the idea to look at existing medications for depression and how they might be repurposed for the treatment of Alzheimer’s disease.
“The R&D costs for a new drug is over a billion dollars and takes more than a decade to get to market, with no guarantees that it will be successful, says Nekkar. “There must be a faster and more efficient way to a cure.”
The determination to dig deeper for answers has been with him since he was a child. “I was the kid who always asked ‘why?’” Nekkar recalls. “To this day, I’m still not satisfied with insufficient answers. I look at data through the lens of a scientist but my colleagues in other fields offer another perspective. Together, we can find unique solutions to the biggest medical problems of today.”
Nekkar’s lab showcases that taking a pragmatic approach to discovery and repurposing drugs already on the market can help people suffering from debilitating diseases like Alzheimer’s get quick and safe access to life-changing medications.
Nekkar’s collaboration with researcher Bruno Bontempi at the University of Bordeaux, France, has yielded promising results. Recently, the research teams were awarded the Bordeaux-Waterloo Grant which is being used for further experimentation with the molecules that Nekkar’s lab has developed.
By sharing information and building on each other’s research, the School of Pharmacy and its international partners are able to draw from a pool of diverse patient samples from around the world, stretch their funding dollars even further and make faster advancements in science.
In addition to the international collaborations, this work demonstrates the power of transformational research connections happening at Waterloo. Interdisciplinary connections between the School of Pharmacy and the department of Mechanical and Mechatronics Engineering are fostering advancements in modelling, screening and tool development.
Working closely with Carolyn Ren, Canada Research Chair in Lab-on-a-Chip Technology, Nekkar and his team developed microfluidic platforms for rapid drug and compound library screening. This technology can identify potential compounds that have biological activity, such as Alzheimer’s disease, and has led to their research being published in the Journal of Analytical Chemistry. This research has also led to collaboration with an industry partner to develop commercial microfluidic platforms for compound library screening.
As Nekkar puts it, “Innovation comes through collaboration and interdisciplinary research.”
Past treatments for Alzheimer’s disease and other forms of dementia have led to an emotional rollercoaster for patients and their families. New medications come to the market and are met with tremendous optimism, only to be followed by disappointment when the medications have little to no effect.
Waterloo’s discovery offers renewed hope. With a decade of research on Alzheimer’s disease completed, the results are unmistakable. Nekkar’s lab has unlocked a way to slow Alzheimer’s in its tracks, giving hope to sufferers and their families as Nekkar and his team work towards a cure.
