Oct 25, 2023

Breakthrough molecule offers hope in fight against ALS

Programs: Graduate, Research: Brain & Neuroscience, Impactful research, Disruptive Innovation, Dynamic Collaboration

Entrepreneurial student aims to bring treatment to patients

Dr. Janice Robertson and Dr. Marc Shenouda
Photo by Kate McDonald
By Jenni Bozec

The death of actress Sandra Bullock’s partner from Amyotrophic Lateral Sclerosis (ALS) earlier this year once again highlighted this disease and the terrible impact it has on patients and their loved ones.

Also known as Lou Gehrig’s disease, or motor neuron disease, it is when the brain and muscles of the body no longer communicate, leading to progressive paralysis. There is no cure and patients usually die within 2 - 5 years of diagnosis. According to the ALS Society of Canada, more than 200,000 people around the world have been diagnosed with ALS, and approximately 3,000 Canadians are currently living with the disease.

Dr. Marc Shenouda recently completed his PhD in the lab of Dr. Janice Robertson in the Department of Laboratory Medicine & Pathobiology at the Tanz Centre for Research in Neurodegenerative Diseases (Tanz CRND). Through his research, the team has recently discovered a molecule that could help provide treatment for ALS and they have received an award from the Connaught Fund to progress this project. Combined with his desire to develop his entrepreneurial skills, Shenouda hopes the team can develop this small molecule into a treatment that can improve the lives of patients with ALS.

The potential to extend and improve quality of life

A protein called TDP-43 is produced throughout our body but in ALS patients it becomes abnormal and starts to form clumps in neurons of the brain and spinal cord. As this builds up, it causes damage, resulting in neurons dying – the main characteristic of ALS. This abnormality of TDP-43 is also found in other diseases that cause cognitive decline such as frontotemporal dementia (FTD) and Alzheimer’s disease. 5 – 10% of ALS cases have a genetic causation for which scientists are developing gene-targeted therapies to correct the disease mutation, but for the rest of the cases, called sporadic ALS, the causes remain unclear.

The molecule discovered by the Robertson Lab (named JRMS-22 - Janice Robertson Marc Shenouda) helps to clear toxic clumps of TDP-43 and prevent them from forming in the first place. “We now have a drug that shows a 40% reduction in TDP-43 clumping within two weeks of treatment in mice. If we can prevent these toxic clumps from occurring, and reverse them, neurons will live longer, which will slow disease progression, extending patients’ lives,” Shenouda explains. They now aim to continue to improve the efficacy of JRMS with the ultimate goal of taking it to human clinical trials.

This discovery could have implications for other diseases where TDP-43 pathology is now being recognised, like Alzheimer's disease and FTD. Similarly in these diseases, the team will need to overcome the challenge of the blood-brain barrier. A defence mechanism of our brain, it is extremely difficult to get therapeutics through as it filters most substances out of the blood. LMP’s Dr. Isabelle Aubert was part of a team at Sunnybrook Research Institute to use ultrasound to pass the blood-brain barrier. The first trial using this technology in ALS patients was recently undertaken by Robertson’s collaborators – Dr. Lorne Zinman and Dr. Age Agessandro.

“One of the joys of working at the Tanz CRND and being part of LMP is that we are surrounded by colleagues working on many different types of neurogenerative diseases and we can learn and share in our discoveries. This network means we will have the incredible opportunity to take our small molecule through to human clinical trials at a local level,” says Robertson.

Using a network to progress to commercialisation

Robertson connected with U of T Innovations Office to discuss the pathway forward, which led to applying for The Connaught Innovation Award: one-time seed funding to ‘support the development and commercialization of U of T researchers’ innovative technologies’.

“Ian Stewart and the rest of the team in the Innovations Office have been terrific in their support – from helping us navigate the system, to making connections and communicating our project,” says Robertson.

The Connaught Award will enable the team to obtain the preclinical data necessary to advance JRMS and find commercialisation partners to progress towards a potential clinical trial. Shenouda and Robertson are currently working with the Innovations Office to submit a provisional patent for this discovery.

Shenouda has tapped into the many resources at U of T to help him develop, research, and learn the skills to commercialise this discovery. He took part in various programs such as the Building a Biotech Venture program at Medicine by Design, Summer by Design program, Lab2Market Launch and Innovation Factory. These helped him develop the skills he needed; from understanding how to pitch to investors, to business strategy and communication. The Health Innovation Hub (H2i), part of the Building a Biotech Venture program and counting Dr. Paul Santerre and LMP’s Dr. Joseph Ferenbok in its leadership, has provided guidance, advice, and mentors. Shenouda also met members of The Association for Frontotemporal Degeneration when networking at a conference who encouraged him to apply (successfully) for their Holloway Postdoctoral Fellowship. He now has two funded years to continue his project in the Robertson Lab as a Postdoc. The many people Marc has met and worked with so far have given him a huge diversity of perspectives and opportunities.

Robertson comments, “This underscores how you cannot do science in a vacuum. Marc has, through his own ingenuity and momentum, developed an incredible network around him that is helping him realise our vision of a cure for ALS. The Connaught Award, particularly, is thrilling. It is a huge recognition of our work and gives us optimism that we're going in the right direction. Awards like this give us visibility and credibility when we’re looking for commercialisation partners as we’re also now endorsed by the Research & Innovation Office at the University of Toronto and the Toronto Innovation Accelerator Program.”

A new way to be a scientist

What this experience has demonstrated to Shenouda is that there is more than one way to be a scientist.

“When I first started my PhD, I wanted a traditional academic career, but I realised that as soon as you start publishing your data in the public domain, pharma companies, for example, aren’t so interested in commercialising it. If I want to bring discovery into the clinic, I need to do the science, but also to be able to ‘sell’ it to business and understand that process. Many scientists are not in a position to do this which means there is a disconnect between discovery and the health industry. I'm trying to bring these two worlds together so we can take innovations like this, get the attention of Big Pharma and attract investors, so we can reach the people who really need it”.

Robertson adds, “It’s also been enlightening for me as a supervisor. I didn’t have these kinds of opportunities in careers or skills development when I was starting out in research so it’s great that I can guide my students in different directions now. Marc is learning and gathering all the tools he needs to start a company so he can drive forward discovery. There is a wealth of support and opportunity in the university for students like him which is incredible.”

This work has been funded by the generous donations of the James Hunter Family ALS Initiative, The Thierry Latran Foundation from ALS Canada/Brain Canada and the Canadian Institute of Health Research (CIHR).

This story showcases the following pillars of the LMP strategic plan: Dynamic Collaboration (pillar 2), Impactful Research (pillar 3), Disruptive Innovation (pillar 4) and Agile Education (pillar 5).