Many young boys look forward to their first soccer game, to the annual summer canoeing trip, or to throwing a frisbee with friends at the beach. However, 1 in 3,500 boys are unable to participate. They rely on wheelchairs to move around, and because their muscles progressively weaken, they are faced with cardiac and respiratory problems. Many don’t live past their late teens. These young boys have Duchenne muscular dystrophy (DMD).
“It’s a muscle disease,” Dr. Bryan Stewart, professor of biology at UTM, explains to me in simple terms. “It only [affects] boys because it’s a genetic problem with the X chromosome.” Girls have two X chromosomes and therefore, will not have DMD unless both their chromosomes have the DMD-mutated gene. “The problem arises because [DMD patients] have genetic mutations in the gene that produce a protein called dystrophin. [Dystrophin] is important for stabilizing muscles.”
Stewart, who researches neurophysiology and muscle physiology, explains that the symptoms of DMD typically appear in early childhood, when developmental milestones such as walking aren’t reached. DMD is a progressive disease which means that symptoms worsen overtime. The risk of fatality is especially high when muscular degeneration occurs in the heart and lungs.
The DMD gene was discovered over two decades ago and there is plenty of literature on drug treatments for DMD. However, despite the extensive research, no cure currently exists. Current drug treatments are limited to focusing on reducing or slowing down the progression of muscular degeneration in DMD patients and, as Stewart states, none of them address the “root” of the disease.
The Stewart Lab is collaborating with the Gilbert Lab in hopes of filling in the gaps present in the current DMD research. They use electrophysiology and human engineered muscle tissue to study DMD cells aiming to discover advances in muscular dystrophy treatments. On January 22, 2020, the Canadian Institutes of Health Research (CIHR) approved a grant to support the two labs’ joint research. The grant will propel the team of researchers forward in their long-term ambition to contribute to an effective overall strategy of treating DMD patients.
In 2016, Stewart met Dr. Penney Gilbert, “a stem cell biologist, and a biomedical engineer,” at the Science Leadership Program conference held at the University of Toronto. After they “realiz[ed they] had things to work on together and different sources of expertise,” they decided to join forces. They also considered whether Christine Nguyen, a Ph.D. student in Dr. Stewart’s lab, “was sufficiently interested to work on [the project],” and because she was, they started their collaboration.
Gilbert’s research at the University of Toronto examines “skeletal muscle endogenous repair.” Her lab “grow[s] motor nerves and muscle in cultures from stem cells,” explains Stewart. “Basically, they’re growing miniature muscles.”
“In a dish,” Nguyen adds.
Stewart’s lab, on the other hand, “works on neurophysiology, muscle physiology, and a lot of development stuff.” With human engineered “miniature muscles” available, courtesy of the Gilbert lab, the Stewart Lab is able to measure the performance of a muscle along with how it interacts with the nervous system “in a way that was impossible before.”
Nguyen provides further details on the actual process: “We get the stem cells from [the Gilbert lab] and bring [them] back here to UTM where I myself also do the generating of 3D tissue. We work in the cell room, we get those stem cells, and we grow them into these 3D tissues.”
“I have healthy cells as well as DMD cells. And the way we measure the activity of the cell is by looking at the [cell’s] electrophysiology. We characterize the electrical properties of the cell, because every cell behaves as an electrical circuit. Understanding the properties of it is important for us to understand how the cells function.”
“And the third thing we do is add drug [treatments],” Stewart continues. “We can compare a healthy [muscle tissue] to diseased [muscle tissue] and compare the before and after drug treatment effect.”
“My lab doesn’t have expertise on stem cell or muscle engineering. [The Gilbert Lab] doesn’t have expertise on physiology and neurobiology. But together we have all the required tools. We couldn’t have started the project without them, and they couldn’t have done the project without us. It’s a true collaboration.”
“And [Nguyen] is the main person on our side,” adds Stewart. “It’s the graduate students doing most of the work.”
Nguyen says that the project is “not [a] typical nine to five job. You have to wait on the cells, and when they’re ready, you have to jump on it because you have a time frame to get things done.”
“It’s bloody hard work—very finicky,” Stewart affirms.
With the approved grant from CIHR, Stewart, Nguyen, and the Gilbert lab are one “baby step” closer to finding an effective treatment strategy for DMD. “We got some support from UTM Principal’s Research Office who provide funding for projects. That helped [us] get off the ground,” Stewart acknowledges. When his lab’s proposal was later approved by CIHR, Stewart recalls feeling “surreal.”
“It didn’t hit him for a few days,” Nguyen laughs. “When he first told me, I was like, ‘Why aren’t you excited? Did it hit you yet?’ and he was like, ‘I don’t think so.’ And the next week I see him just smiling, and I’m like, ‘It hit you!’”
“Because the success rate [of receiving CIHR funding] is so low, you can never really expect to get it. That’s not to say our research is better than other research. There is a ton of good non-funded research.” The CIHR funding will support graduate and postdoctoral student salaries and help the lab purchase equipment and necessary supplies. Essentially, “the funding allows us to do the work,” says Stewart.
“In the end, we’d like to think what we’re working on will contribute to an overall strategy of treating DMD patients. That could include drug therapies, it could include stem cell therapies, or [it could include] gene editing technologies,” explains Stewart.
“We’re also aiming to do something like personalized therapies. If you had DMD, we’d be able to go in, take your stem cells, make your muscles in a dish, and test different drugs treatments that might work for you, [but] might not work for others,” Nguyen adds.
“But all that stuff is a long way down. [Essentially,] the eventual [goal] is to try and help people.”