April 11, 2021  | ITN Communications 

With brain diseases as the leading cause of disability in Canadians and an aging population in the country, researchers are racing to find treatments that will help nearly 3.6 million Canadians affected by a brain condition.

Drugs that treat the symptoms of Alzheimer’s, Parkinson’s and other neurodegenerative diseases haven’t had a breakthrough in decades. These complex brain diseases have challenged researchers working on drug therapies, while pharmaceutical companies have stopped investing in new treatments due to prohibitive costs and high rates of failure.

Recognizing the need for a new approach to testing drugs for neurodegenerative diseases, a joint team of researchers from Western University and McGill University and are working together to create a multi-step procedure to better evaluate the performance of drugs during lab testing. The project aims to predict which drugs may become successful in clinical trials. The multi-step system will allow for drugs to be tested more effectively and efficiently, reducing the chance for failures in later testing stages.

“We want to increase the success of drugs that move from the preclinical or animal phase of testing to human trials,” said Dr. Marco Prado, Canada Research Chair in Neurochemistry of Dementia and professor at Western’s Schulich School for Medicine & Dentistry. “We realized there are better ways to be more robust and rigorous with drug testing.”

Dr. Prado has teamed up with Dr. Mallar Chakravarty, computational neuroscientist and Director of the Brain Imaging Centre and the Neuroinformatics Platform at the Douglas Research Centre, to combine the research strengths of both McGill and Western. This collaborative project is possible because of the newly developed McGill-Western Initiative for Translational Neuroscience (ITN), supported by the Canada First Research Excellence Fund (CFREF) through McGill’s Healthy Brains, Healthy Lives and Western’s BrainsCAN initiatives.

Bridging the gap

The project involves a thorough investigation of drugs at the preclinical stage using advanced brain imaging techniques and cognitive tests for memory, learning and behaviour―the most sophisticated method of testing the success rate of a drug to date. These behavioural tests and imaging techniques are first used on animals, such as mice, and the exact same tests are applied later to humans.

As Dr. Prado explains, the ability to measure a drug’s success in animal models is dependent on the relevancy of the tests in humans.

“There’s been a lot of research using tests that worked really well in animal models, but those tests are not applicable to humans,” said Dr. Prado. “Luckily, we can do tests that are similar between humans and animal models, and we can use imaging techniques that are similar between humans and animal models. The idea is to try to make all of our steps directly translate to humans.” 

To administer these tests, renowned Western researchers, Dr. Tim Bussey and Dr. Lisa Saksida have developed a touchscreen-based system allowing researchers to test both animals and humans using a video game on a tablet. This ensures that memory, learning and behaviour deficiencies seen in test results from animal models are similar to the issues detected in humans with brain diseases.

At McGill, Dr. Chakravarty’s lab is working on advanced brain imaging techniques to evaluate a drug’s success in the preclinical phase.

“Small animal magnetic resonance imaging (MRI), especially in mice, is an emerging field and technique. MRI provides the opportunity to examine how the brain changes over time in the same animal and in response to drugs,” said Dr. Chakravarty. “Our lab has been working to make this a reproducible and sensitive technique that can be used in animal models.”

If a drug has positive results across imaging and cognitive tests with animals, it signals that the drug might work well when it comes to human trials.

Transforming drug evaluation methods

Overall, this drug evaluation procedure may save hundreds of millions of dollars by identifying which drugs will fail during animal testing and therefore avoid ineffective clinical trials. This procedure may also help to speed up the evaluation of whether a drug will be successful in humans, resulting in quicker access to treatments for those experiencing symptoms of brain diseases.

Dr. Prado also explained that the omission of pharmaceutical companies in the review process will also keep the study of the drugs as impartial as possible. “This project allows us to be rigorous with the research, while using unbiased technology and arms-length evaluations. If a drug fails in the preclinical stage, it will stop right there and there would be no interest to move it forward.”

To expand the impact of the project, the researchers will use an open science framework—which Dr. Chakravarty explains will make the data widely available for researchers and clinicians around the world.

“By making our tools and data available, other laboratories can use our technology or re-evaluate our findings,” said Dr. Chakravarty. “In the hands of other skilled colleagues, we may learn something new from our older data.”

With the creation of a radical new drug evaluation process for neurodegenerative diseases, researchers at McGill and Western hope to transform the way drugs are evaluated prior to human trials. Ultimately, the goal is to use this drug evaluation method to find new ways to cure neurodegenerative diseases.

“Our goal is to establish a clear path forward for a novel way to consider the testing of new drugs,” said Dr. Chakravarty. “Our work seeks to establish promising leads so that we will be able to identify drugs with best potential for moving to clinical trials in humans.”

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The McGill-Western Initiative for Translational Neuroscience (ITN) is a collaborative research initiative supporting two large-scale research projects to impact the lives of those living with neurodegenerative conditions. Supported by the Canada First Research Excellence Fund (CFREF) through Western’s BrainsCAN and McGill’s Healthy Brains, Healthy Lives initiatives, the ITN brings world-renowned neuroscientists from McGill and Western together to focus on neurodegenerative research projects.