Democratizing access to state-of-the art tools, accelerating innovation

By Alison Palmer, Evaluation and Special Projects Lead 

Imagine a neurosurgeon using light or sound to manipulate specific cells in your brain and restore your brain health. 

Instead of implanting electrodes and buzzing broader areas of your brain to help relieve symptoms of Parkinson’s disease, for example, a neurosurgeon would use gene therapy to deliver light-sensitive proteins into specific brain cells affected by the disease and use light to stimulate only those cells. The result would be restored function, with a reduced risk of adverse effects. This same approach could be used to deliver the relief of an epidural in an on-demand, targeted way to the part of your body experiencing chronic pain.

“It sounds like science fiction, but our platform is trying to turn this into reality,” explains Dr. Yves De Koninck, Principal Investigator of the Canadian Optogenetics and Vectorology Foundry, a Brain Canada-supported platform, and professor at l’Université Laval. “It’s the ultimate neurostimulation approach.” 

The field of research, called optogenetics, combines genetic engineering with optical technology. It generates light-sensitive proteins, introduces these into cells via viral vectors (deactivated viruses specifically designed to deliver genetic material encoding these proteins into cells), and uses custom designed sensors to both control and monitor what happens in those cells in real time. The next frontier of this revolutionary research is developing sound-sensitive proteins that would work sound in the same manner.  

The promise of optogenetics 

The field is advancing rapidly and according to co-principal investigator Dr. Marie-Eve Paquet at l’Université Laval, it will bring some of these therapeutic benefits in the coming decade.  

“Optogenetic tools are already being used to treat certain eye diseases,” she explains. And optogenetic-based treatments for pain relief have been successful in mouse studies. There are many technical challenges to overcome, including scale up and testing in non-human primates. 

“Our platform’s ability to maintain high standards and support R&D to address these challenges is made possible with the sustained funding provided by Brain Canada.” 

The Brain Canada-funded team at the forefront of this field includes 14 investigators from six universities across the country, bridging expertise in protein engineering, imaging, animal models, clinical practice, and neuroendocrinology. Now in it’s second iteration, the Canadian Optogenetics and Vectorology Foundry platform is focused on laying the groundwork for therapeutic applications.  

“We are among the only teams bridging the gap between the academic production of viral vectors and the clinical setting,” explains Dr. Paquet. “Our model of rapid customization and distribution of tools allows researchers around the world to quickly access and test new innovations.” 

What’s the impact?

The viral vectors that Dr. Paquet and the team are developing are in high demand for advancing optogenetics; over the last three years, they shipped more than 1,300 of these products to more than 250 research labs across Canada and around the world. With a design-build-test-learn cycle at the core of the platform, the team has conducted significant research and development to advance the technology. Together, they’ve generated more than 120 scientific publications since 2021. The researchers applying the products and services of the platform generated another 100+ publications, accelerating our understanding across a broad range of brain research topics including sleep loss, locomotion, eating disorders, and heat exposure. 

At the Centre for Brain Health at UBC, we benefit greatly from the customized vectors the Foundry platform develops. We’ve received more than 50 vectors over the past 8 years, shared across several research teams, which we’ve used to uncover synaptic and network changes underlying brain disorders such as stroke, Huntington’s, and Alzheimer’s disease. These vectors are unique assets that allow us work at the frontier of neuroscience, which is evolving very quickly.

Dr. Shernaz Bamji, Co-Director of the Center for Brain Health at UBC and Brain Canada Board Director.

What makes these viral vectors particularly attractive to research groups is the fact that they’re produced rapidly at a small-scale and are custom tailored to the researchers’ needs. Research groups include innovation-focused industry partners, whose business is made possible by the platform.  

To date, the team has partnered with six of these companies including IVANO Biosciences, which is using the vectors to evaluate the effectiveness of vaccines. Another partner, Cerebro Therapeutics, is using the vectors to prevent the aggregation of alpha-synuclein, the protein that misfolds and accumulates in the brain of people diagnosed with Parkinson’s disease, and halt the disease progression. 

On the hardware side of the platform, which goes hand-in-hand with the viral vectors, the team has filed eight patents for various devices and research methods developed and obtained four licenses since 2014. A series of spin-off companies have resulted, including Bliq Photonics, which was started by two former graduate students supported by the platform.  

Bliq Photonics, a Quebec City-based company that employs 18 staff, is developing custom microscopes and other hardware that complement the platform’s needs. The partnership provides the platform researchers access to specialized engineering expertise and hardware tailored for things like optogenetic control, real-time sensing, and high-resolution imaging in neuroscience.  

Brain Canada-funded platforms – a pillar of open science

As Dr. De Koninck notes, the team is striking an important balance between commercialization and open science. 

“We’ve protected many of our discoveries on the hardware side of things, but we’ve been intentional about democratizing access to the new genetic tools the platform is developing,” explains Dr. De Koninck. “We want to be sure that we’re accelerating the transfer of this work and preventing obstacles on the path to clinical applications.”  

For example, they collect fees for the vectors but with an eye to accessibility, and giving Canadian researchers a competitive advantage, they’ve offered discounts for early-career researchers and Canadian laboratories. These discounts are made possible through the platform support, as well as the more than 20 grants and over $45 million the team has obtained to leverage and build on that support. 

“Brain Canada’s role has been exemplary on this front – if we want to advance open science, platforms are the pillar,” explains Dr. De Koninck. “The funding from Brain Canada has allowed this platform to operate at a scale, flexibility, and quality that is driving innovation and advancing research in transformative ways. It’s a model that other countries are trying to emulate.” 

“This kind of dedicated platform-level funding is very rare in the scientific community,” adds Dr. Paquet. “It’s been very impactful.” 

Links

Stuart Jantzen, “Recording the Illuminated Neuron” animation

Principal investigators Drs. Yves De Koninck and Marie-Eve Paquet along with co-investigators Drs. Paul De Koninck, Robert Campbell, Keith Murai, Ed Ruthazer, Stuart Trenholm, Reza Sharif-Naeini, Thomas Durcan, Tomoko Ohyama, Edward Fon, Jean-Claude Béique, Stephanie Borgland, and Lynn Raymond were awarded a $4.3 million Platform Support Grant (PSG) from Brain Canada in 2019 to advance the Canadian Optogenetics and Vectorology Foundry. This grant built upon a previous iteration of the platform, also supported through the PSG program starting in 2014. The PSG 2019 grant was made possible with the financial support of Health Canada, through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and the Djavad Mowafaghian Centre for Brain Health, Université Laval CERVO, McGill University, University of Calgary, and University of Ottawa.

Read More: Major boost to brain research with new $4M grant to help advance the field of neuroscience