This first-of-its-kind platform brings together a series of cutting-edge tests focused on evaluating how potential therapies impact cognition, such as memory, thinking skills and learning, from cell cultures to animal models. It will also study high-quality disease biomarkers and brain imaging, leveraging Western's innovative cognition testing platforms, advanced molecular and imaging techniques and existing industry and academic partnerships. A thorough consideration of sex and gender will also be included, as therapies often work differently in men and women.
“We are creating a one-stop shop to identify and predict the success of drugs in human trials faster and cheaper,” - Ravi Menon, scientific director of the Centre for Functional and Metabolic Mapping (CFMM).
“By putting appropriate testing models together, with the best technology and world-leading experts under one roof, we’re going to make it less risky to develop treatments for these brain diseases, we’re going to save a lot of money, and we’re going to get effective therapies to patients faster,” said Menon.
Neurodegenerative diseases are a growing concern globally. According to the Public Health Agency of Canada, annual healthcare costs for Canadians affected by dementia alone are expected to reach $16.6 billion by 2031, doubling what was spent two decades earlier.
However, the number of therapies in the pipeline for these disorders is meagre and drug development is expensive and risky: It can cost more than $50 million to bring a single compound to clinical trial and more than $1 billion to move forward to market approval.
Menon's new platform aims to narrow the gap across the “valley of death” – the crucial phase between lab testing and human trials of drugs and their subsequent commercialization, where most compounds fail. This will be achieved by focusing on the fundamental aspect of neurodegenerative diseases often overlooked – cognition.
“Neurodegenerative diseases impact cognition – mental processes that enable us to carry out everyday tasks, solve problems, make decisions, and interact with our surroundings. However, millions of dollars are invested in developing drugs without evaluating their impact on cognition and invariably, the human clinical trials of such drugs fail,” said Menon, professor of Medical Biophysics, Medical Imaging, Neuroscience and Psychiatry.
Researchers will focus on evaluating cognitive functions such as memory, learning, decision-making and attention in a variety of ways. This will include analyzing special lab-grown cells from patients that mimic the human brain-- called brain organoids-- advanced brain imaging, as well as the use of touchscreen technology developed at Western to test the efficacy of drugs on cognition across species.
Professor Ravi Menon, Schulich School of Medicine & Dentistry and Professor Lisa Saksida, Tier 1 Canada Research Chair, Schulich School of Medicine & Dentistry (Photo: Schulich Communications)
“Western is leading the way in creating groundbreaking, non-invasive methods to study cognition, including the use of touchscreens. With this technology, we can delve deeply into complex cognitive processes like planning, decision-making and attention across different animal species, with tasks identical to those used in humans. This gives us crucial insights into the inner workings of the brain,” said Lisa Saksida, a co-investigator on this project.
“Our expertise in this area will be crucial in assessing drugs for neurodegenerative diseases in ways that have never been attempted before.”
A Schulich Medicine & Dentistry professor and Tier 1 Canada Research Chair in translational cognitive neuroscience, Saksida has worked with Tim Bussey, Western Research Chair in cognitive neuroscience, on the development of a touchscreen-based cognitive assessment system specifically for mouse models since 2000. Touchscreen testing is now regarded as a best practice by the international research community to test cognition in animal models.
The subsequent vital phase in drug development involves combining touchscreen testing findings with data from sophisticated brain imaging systems.
“Western is a leader at fostering the interdisciplinary research collaborations necessary to push the boundaries of innovation and to address the world’s most critical health challenges," said Bryan Neff, Western’s acting vice-president (research). “We are grateful to those who have partnered with this initiative and to the Government of Canada for their continued support of transformative research that allows us to have greater impact in communities at home and around the world.”
Western’s Mouse Translational Research Accelerator Platform in the Schulich School of Medicine & Dentistry houses the world’s largest collection of touchscreen testing systems, integrated with sophisticated neurotechnologies. Western's CFMM at Robarts Research Institute has Canada's national ultra-high field MRI platform. This cutting-edge equipment enables researchers to capture precise brain images, essential for comprehending its functionality and the impact of diseases on it.
With its nucleus at Western, the multi-centre project - called TRanslational Initiative to DE-risk NeuroTherapeutics (TRIDENT) - is in collaboration with McGill University, University of British Columbia, University of Toronto, the Centre for Addiction and Mental Health, the Douglas Research Centre and a number of international partners, including the U.K. Dementia Research Institute.
Transparency is one of the key priorities of the platform. Based on open science principles, the platform will ensure failures are public and knowledge is shared, providing valuable insights to the wider scientific community. All data will be deposited in the group’s open access database MouseBytes.
“By sharing data, knowledge, materials, and tools with the global scientific community, TRIDENT will foster collaboration and enable researchers to learn from both successful and failed trials. This open approach will accelerate the drug discovery process,” said Saksida.
Researchers hope they will be able to identify many drugs that will be successful in human trials within six years.
“By leading real and lasting change in the way therapies are tested for neurodegenerative disorders, we hope to dramatically improve their chances of success in clinical trials and benefit millions of patients,” said Menon, who is also co-scientific director of BrainsCAN, along with Saksida.
The full version of the release can be read here.
The TRanslational Initiative to DE-risk NeuroTherapeutics (TRIDENT) draws upon research supported by the Government of Canada’s New Frontiers in Research Fund (NFRF).
TRanslational Initiative to DE-risk NeuroTherapeutics (TRIDENT) repose sur des recherches financées par le fonds Nouvelles frontières en recherche du gouvernement du Canada.
