Talking Real Science with Chris Perry

This episode of Share Science features Christopher Perry, PhD, an associate professor at York University’s School of Kinesiology & Health Science. Chris’ laboratory investigates the regulation of skeletal muscle metabolism and focuses on developing therapies to improve muscle fitness in rare muscle disorders and in cancer and chemotherapy-induced muscle weakness. In this podcast, Chris not only shares his career path, but also his ideas and goals of creating a contract research organization (CRO) to further help those with muscle disease and to provide more opportunities for his trainees.

I grew up in a few small towns outside of Toronto, usually within an hour. What I remember as a boy was my mom buying me books on astronomy, stars, and planets, and I very quickly decided one day I’d be an astronomer. Then I got into high school and one way or another started to become really fascinated with how the body works.

I don’t remember that transition at all, but I do remember a conversation at the end of high school with my guidance counselor. He said, “What are you interested in?” I said, “Well, human physiology, exercise science,” and he said, “Have you ever heard the word kinesiology?” I said, “No,” and he said, “You should look into that.” I did, and I just felt that excitement. That’s what I wanted to learn about. I wasn’t too sure what I wanted to be, but it was Mr. Jones at Acton High School who said, “You should look into kinesiology.” Now I’m in the School of Kinesiology at York University. I actually connected with him a few years ago and told him that story. That would be a big influence on me.

As a fourth-year student in human kinetics at the University of Guelph, I wanted to see what research was about. I did a research project with Professor Brian Wilson, who’s now retired, and he was full of enthusiasm, and still is. He had these ideas for looking at how exercise affects the ability to improve your run time to performance, and using whole body measures with a little bit of blood samples for things like VO2 max.

“For me, I had no idea research could be … yelling at someone on a bike. I thought it would just be sitting in this little dank lab, like first-year chemistry, mixing this chemical and that chemical and your assignment was to describe what the color change was and why that was. … I got to see what human research can be.”

He took me on as a master’s student, and I loved it so much that I wanted to delve more into the mechanisms by which our fitness is determined, so I did a PhD with Professor Lawrence Spriet in the same department. He also did applied research, but he added muscle biopsies to that and taught me biochemistry, how to understand the regulation of very specific metabolic pathways in muscle that convert food into energy.

“I did a thesis on how exercise improves the regulation of skeletal muscle metabolism in humans. I was hooked. I was absolutely hooked. I thought, “Okay, this is what I want to do. I think I want to be a professor. I’m not sure, but I know I love this.” I went with what I love.”

I wanted to delve more deeply within mitochondria. I also now wanted to understand how muscles get worse. I felt like I had a pretty good grasp on how muscles get better: when you stress them with exercise, you improve their fitness. I wondered if I could learn more about how to conduct clinical research on diseases that make muscle fitness decline, and I also wanted to learn how to do preclinical research in cells and rodents. I did a postdoc in North Carolina with Professor Darrell Neufer and learned both of those. I was exposed to clinical research on how overnutrition, overeating, and sedentarism leads to insulin resistance which can eventually lead to type 2 diabetes.

When I came to York as faculty, I had all these plans to pursue both of those topics: exercise and type 2 diabetes. I went to a presentation on Duchenne muscular dystrophy and metabolic dysfunctional muscle, and I realized I don’t know anything about muscle weakness disorders. I wondered if there was an opportunity to move sideways with the expertise I had at the cellular level and then move up in various diseases, so to speak. Diabetes and exercise were my expertise, but how creative could I be in applying that to determine two things? One, the degree to which there’s mitochondrial stress in various diseases that are receiving very little attention but are linked with a theme of muscle weakness. Two, can we translate those discoveries into preclinical therapeutic development approaches?

“Once we discover specific metabolic pathways that are irregular … in muscle from a muscle weakness disorder, how would I ever go about testing or perhaps developing new compounds at that preclinical level? It was an evolution over the years that brought us to where we are today.”

To study a muscle weakness disorder, you need a system that measures force production within muscles. There are whole body approaches, and then there are in situ and in vitro. Aurora’s system is absolutely essential for determining whether or not a drug that we are testing in a rodent prevents muscle weakness. We also add whole body measures such as grip strength or various treadmill tests. The challenge with those tests is that they’re subject to the choice of the mouse to continue or to stop. There are ways to motivate ethically, but at the end of the day, they also have a behavioral component. When you think about the diseases we’re studying, you wonder what level of discomfort the mice are feeling.

“Maybe they’re just not motivated to exercise. Does that mean they have muscle weakness? How do you determine whether … reduced physical activity in any of these tests is actually due to weak muscles or some other factor like pain?”

It doesn’t mean that we exclude those tests; we do them, but we then add on muscle-specific force majeures. The Aurora system was the one we started with, and it’s just the best and it’s broadly known. It’s been transformative: in fact, we’ve got one drug, one partnership that’s using that system, that appears to be preventing weakness in the diaphragm by up to 30% in mice with Duchenne. If we didn’t measure muscle force, we wouldn’t know that.

All of our industry partnerships to date have been a result of either me reaching out to a company that had a pipeline or compound already in existence that mechanistically had the potential to correct these dysfunctions, or they had heard of our work and approached us. It’s so exciting to work with industry partners. So far, most of that’s been pharma.

When we approach, sometimes there’s interest and sometimes there’s not, or we think is this something that we can expand? Is there an approach to bring more of those opportunities along? This has been so productive and so exciting, and I’d like to see more of those opportunities come. The question is, do we just keep going along or do I bring it to the next level somehow?

“There are probably people listening to this that have already done this and know about it … please reach out to me because I’m at the learning stage.”

My only thought so far, even though I’m not sure if a CRO would make a big difference, is the factors I’m looking for and the factors I’d like to learn about. Will it accelerate discovery, an identification of new potential therapies that is following a process that works for progression to clinical trials with industry partners? You can discover a compound, and you can probably go buy any compound that you want that’s commercially available and tested, but how are you going to progress that to actually test the people? You need industry and clinical partners.

How does a CRO bring those all together? Is it just marketing and branding, or are there other factors? Will it also bring in more resources, people, technology, and funding? I’m learning about that, but in all of this, it also has to achieve the second objective of helping the students.

“Students are number one right up there with the discovery, and the feedback I’ve gotten from the students is they love to see someone that’s not just in our group, and that wasn’t a negative. I’m actually paraphrasing them. As far as I know, they’re pretty happy in the lab. They say they’re happy in the lab, but the value to the students has been to fly to a company, to Zoom with a company, to meet a clinician.”

Now, I could just have meetings with these partners, but why would I do that? First of all, I can’t remember everything they remember–they’re the experts. Secondly, this is an opportunity for a student to learn with me about the translation process and build networks. One student was flown down to the United States to meet a company partner and in the evenings, they got to speak with medical science liaisons who weren’t part of our collaboration, and they learned about careers they didn’t know before. Why wouldn’t I keep doing this? If a CRO brings more of that for the students, so long as it doesn’t take away the experience that we currently have with our system, then this is good. I think it will just bring more in. Long answer about my uncertainties, but two guiding principles.

This is a brand new thing for us, and we are really excited about it. Each of these steps has been something new for me. We’ve been funded by not-for-profits in the past, private philanthropic foundations, and that’s been interesting to see what they prioritized and to whom they’re accountable. Our latest experience with not-for-profits is with Muscular Dystrophy Canada, an advocacy group raising awareness for people with neuromuscular disease, not just Duchenne. Muscular Dystrophy Canada also does knowledge translation activities and keeps patient communities up to speed on the latest research for emerging therapies in their specific disease.

We’ve received funding graciously from Muscular Dystrophy Canada because they do enormous fundraising efforts from various donors. We were also able to obtain match funding from a federal program called Mitacs that’s focused on providing funding for trainees to gain internship opportunities with not-for-profits and industry. What this means is Muscular Dystrophy Canada is currently funding our research while Mitacs is funding students to work with Muscular Dystrophy Canada outside the lab, away from the bench, with the patient communities, and we’ve never done this.

For example, one of these activities is knowledge translation, in which the students develop newsletters using their expertise to help Muscular Dystrophy Canada summarize latest research discoveries for the patient communities. Another opportunity is creating webinars with Muscular Dystrophy Canada not just behind the scenes, but having the students upfront and meeting the patient communities. Rather than just going to conferences where patients speak, now we can actually interact directly with them through these activities, which is amazing.

“The team at Muscular Dystrophy Canada is so intrinsically motivated when you talk to them. … They want to see their efforts make an impact. … I just can’t tell you how excited I am about this, and that’s our latest.”

Our latest experience is incorporating not-for-profits into this in a way that not only brings trainees to the patient communities, but also allows students to see how a not-for-profit works. They will see how advocacy works. They will see how to translate complex knowledge to a target audience more so than they do already through conferences. It’s also about the students being exposed to the team at Muscular Dystrophy Canada, and I’m learning with them. I better stop talking. I’m so excited about this, but I don’t know what benefits will come. I think I know. I think you know, but I know we will see benefits we didn’t see coming. I think it’s going to be great.