The next medical frontier: Mitochondria are set to revolutionize disease treatment

Many degenerative diseases and chronic conditions have a variety of treatment and/or therapy options. But a group of Canadian scientists is discovering there may be a single solution for many of them: mitochondria.

The energy-producing structures within cells, mitochondria play a critical role in cellular health and function. Now, thanks to recent funding from a New Frontiers in Research Fund Transformation grant, an interdisciplinary team of experts in bioengineering, chemical engineering, artificial intelligence (AI), public health and clinical research has a chance to redefine how the world treats conditions like organ failure and chronic inflammation, as well as degenerative diseases.

The “MitoRevolution” research initiative was recently awarded $23.8 million over six years. The funding will support development of a therapeutic approach that delivers healthy mitochondria directly into damaged cells, promoting regeneration and recovery.

“Mitochondria are the engines of life,” says Ana Andreazza, a University of Toronto professor in pharmacology and psychology, and the nominated principal investigator on the project. “To make an analogy, you can press as hard as you want to turn on your computer, but if it’s not plugged into electricity, your computer will simply not turn on. That’s the level of necessity.”

Andreazza’s research has already advanced the understanding of mitochondrial dysfunction’s role in mental illness, especially mood disorders, as well as the effectiveness of supporting mitochondrial health as a form of therapy. She is thrilled to take things to the next level: exploring mitochondrial transplantation as a possible treatment for a wide range of diseases.

An emerging field

Mitochondria as a treatment is “incredibly exciting,” says Unity Health Toronto scientist Ori Rotstein, a co-principal investigator. Rotstein will oversee integrating the therapy into clinical trials.

“Mitochondrial transplantation was considered a niche treatment, intended for people who had a genetic mitochondrial disease,” Rotstein says. “What we’re providing is a proof of concept and a pretty feasible argument for saying, ‘Okay, it’s not just for this niche group. It’s actually for a broad range of patients and their diseases.’”

University Health Network scientist Sowmya Viswanathan, another co-principal investigator, says she hasn’t seen a consolidated approach like this anywhere else, and will fulfil two roles on the project: chronic disease researcher and regulatory liaison.

"It’s really very new for the regulators as well, so we want to work with them to help them understand this technology, to see if the policies and the regulations that are currently in place are suitable for being able to properly regulate this, or if we need additional checks and balances and what that would look like,” Viswanathan says.

What’s next

The team’s first challenge is to find a readily available source of mitochondria, which are found in blood platelets.

Andreazza explains, “Platelets are discarded by Canadian Blood Services when they expire, but the mitochondria are possibly still alive. So that’s the first milestone of this grant. Can we use these resources that are going to waste … to extract mitochondria and create a new product?”

Another challenge will be how to preserve and deliver the mitochondria, since they are only viable for a maximum of two hours once removed from the cell. The team will use AI to explore different options for preservation.

“Using AI to better understand the optimal surface of the mitochondria will help us be able to store it for up to seven days, maybe even longer,” Rotstein says. As a trained surgeon, he imagines a future where emergency rooms will have mitochondria readily available for patients suffering from heart attacks, strokes or other acute diseases.

The potential wins

Mitochondria dysfunction is at the root of “so many diseases,” Andreazza says, that it’s hard to know how many people could eventually be helped by this treatment.

One area the team believes they’ll be able to make a difference in is organ transplants. Injecting mitochondria into donated organs has been shown to boost the quality of those organs. This would create a larger pool of available organs, shorten waitlist times and improve the number of successful transplant procedures.

“That’s our first achievable goal,” Andreazza says. “We want to make sure that no donated organ goes to waste.”

Given the wide range of potential applications, the team will also use sophisticated organ-on-a-chip devices—mini representations of a human organ—for testing purposes.

“In this project, we have the cardiac chip, lung-on-a-chip, and for myself, knee-on-a-chip,” Viswanathan says. “It’s a really valuable research tool that we’ll use across our individual labs, because we have so many things that we want to test.”

Viswanathan is also excited for the project to make headway on chronic diseases, which she says is long overdue.

“Although we’ve been researching osteoarthritis for many decades, there’s really nothing out there that is curative,” she says. “People ultimately just go for joint replacement surgery, and it’s a very big burden on the health-care system, especially with an aging population.”

Throughout the course of their project, the MitoRevolution team will work with regulators, patient groups and other stakeholders to increase awareness of the mitochondrial transplant option, and to make it widely available.

“The goal for the end of the project, in six years, is to have a product available through Canadian Blood Services that can be used for any patient that needs it,” Andreazza says.