How treatments go from lab to bedside
Why scientific breakthroughs can take years to become available clinical treatments
Last year, multiple headlines saying stem cells could become a cure for blindness ran in newspapers just like this one. I read each story closely, because my research was the subject at hand.
Together with Faculty of Medicine professors Derek van der Kooy and Cindi Morshead, and a large team of scientists and engineers at the University of Toronto, including Brian Ballios and Michael Cooke, we made a breakthrough in stem cell transplantation.
We created a gel-like biomaterial known as a hydrogel that helps transplanted stem cells survive, integrate and repair damaged tissue in the brain and eye. We injected photoreceptor cells — cells in the back of the eye that are responsible for vision — that are derived from stem cells and encapsulated in our hydrogel into the retinas of blind mice. We were able to restore vision by approximately 15 per cent.
The media were right to get excited. We partially reversed blindness. What an incredible accomplishment and further evidence of the therapeutic promise of stem cells.
Yet here we are more than a year later, and there’s still no cure. For many people with macular degeneration, or any degenerative disease for that matter, studies such as mine often produce a lot of hope, but also frustration that the “product” is not available to them.
So why does it take so long for a study like mine to turn into a clinical treatment? Let’s take a closer look. It took us almost a month to grow the right cells before we could inject them into the retinas of mice. This was after years of research. We published promising results, but know that we need to do more research and more development before we can move to clinical trials in people.
Right now, we’re focused on creating better cells to transplant. This will take time, more funding and a lot of testing.
We estimate it will take another three years before we’re ready for clinical trials in humans. But then our work will have to go through strict regulatory controls. We must show that we know everything possible about the materials with which we’re working and there are compelling data to suggest the treatment will be beneficial to patients and won’t cause any harm. To get approval for the clinical trials, we also need to know how to scale up and manufacture our product in a consistent way. This again takes resources: time, money and expertise.
In order to have sufficient quantities to test in people, we must understand how to create and manu- facture our optimized cells reproducibly. This requires expertise in cell manufacturing and quality control — something that Torontobased non-profit organization CCRM, a leader in developing and commercializing regenerative medicine, cell and gene therapy technologies, can fulfil. By combining U of T’s know-how in basic science with CCRM’s in manufacturing, we can develop a reproducible and safe product to test in clinical trials.
Once we get the green light from Health Canada, we can move onto clinical trials to test for safety (phase 1) and efficacy (phases 2 and 3).
It takes13 months on average just to get one site ready for a clinical trial. It can take years more to go through the required phases of clinical trials before bringing a product to the market, depending on how many people register for the trial,
Cost still matters, even at this point. Venture capital is a big challenge in this field. These studies require a lengthy investment process, which means persuading people to fund something that might take many years before they see any returns.
Regenerative medicine is not like the tech industry. When we’re dealing with human lives, we can’t whip up an app to solve a problem. When all is said and done, it can take up to17 years or more to move research from the lab to the patient.
Studies like mine are important because in the case of some diseases, such as age-related macular degeneration and stroke, our current medicines only slow the progression of the disease. Stem cell-based therapies provide the chance to change the way medicine is delivered — that is to stop disease progression and, in the case of blindness, reverse it.
Cells will be the next generation of drugs, but they are complicated by the fact that they are living. It’s one thing to create cells to treat illness; it’s quite another to get those cells to the right places in the body for them to be effective.
We’ve proved that hydrogels can support the survival and integration of stem cell-derived photoreceptors after they are injected. The body can often be a hostile environment for stem cells, and one of the biggest challenges in regenerative medicine is keeping transplanted cells healthy enough to repair the damaged tissue and restore function.
This discovery shows the power of engineered biomaterials to promote healing in the eye and the brain.
The promise of making a difference in someone’s life is great motivation for me to get up and tackle these enormous challenges in human health.
Working with engineers, scientists and surgeons, I am optimistic we will deliver on the promise of regenerative medicine — but it won’t happen right away.
Get involved: If you’ve read about a study and are interested in taking part in a clinical trial, visit clinicaltrials.gov and search for studies by country, using the search term Canada or Toronto. You can see studies based on illness within each province.
If you are not interested in taking part in a clinical trial (or perhaps aren’t eligible), you can still get involved in funding either research at academic institutions or commercialization efforts through venture capital or angel investor networks. Molly Shoichet is a professor at the University of Toronto’s Department of Chemical Engineering & Applied Chemistry, and the Institute of Biomaterials & Biomedical Engineering. She is cross-appointed to the Faculty of Medicine. She holds the Tier I Canada Research Chair in tissue engineering. Doctors’ Notes is a weekly column by members of the U of T Faculty of Medicine. Email: doctorsnotes@thestar.ca.