SCAR WARS: A world centre for fibrosis research
St. Michael's is revolutionizing treatment for fibrosis, or organ scarring, the cause of nearly half the deaths in the developed world.
Diabetes is one of the fastest growing diseases in the world and can cause scarring of the kidneys. Fibrosis (which means scarring of any organ) is responsible for nearly half of all deaths in the developed world.
Forty-five per cent of all chronic diseases in hospitals are related to fibrosis, and it is at the root of most types of heart and kidney failure. Medicine has yet to figure out how to diagnose and treat the problem.
So we are building a world-leading centre for scarring research at St. Michael’s.
At the helm is Dr. Richard Gilbert, a Canada Research Chair in Diabetes Complications and co-founder of Fibrocor, a biotechnology company working on anti-fibrotic therapies. He is leading a multi-disciplinary team of preeminent clinician-scientists with a mission to eliminate kidney scarring. One team member is Dr. Andras Kapus, who is focused on basic science. Another is Dr. Kim Connelly, a cardiologist who studies the effects of diabetes on the kidney and the heart.
The team is a unique collaboration of clinicians and scientists, rare in the world of large hospitals. Together they are taking discoveries from the lab to the clinic, inventing diagnostic tests and developing new drug therapies. The Holy Grail is a treatment that can stop or even reverse scarring.
DRUG THERAPIES TO PREEMPT DEADLY SCARRING
Two promising anti-fibrotic drugs are ready for the next phase of development. The first drug, FT011, has already been shown to be safe in humans. The next stage is a clinical trial involving people with diabetic kidney disease, the leading cause of kidney failure in Canada. The trial began in 2019.
“We are maybe one of half a dozen research groups that started with an idea and progressed that idea right through to a clinical trial,”; says Dr. Gilbert. “It takes a long time. This is 16 years of work.”
Another drug, known as FCR656, aims to preserve the function of transplanted kidneys. All too often, donated kidneys deteriorate and eventually stop working. The cause is chronic allograft nephropathy (CAN), a condition that replaces normal kidney tissue with scarring.
Until now, there have been no drugs to prevent or treat scar tissue formation. But in early studies with mice, FCR656 prevented excess scar tissue from forming. The next step is taking this transformative discovery to human studies.
But without funding, the future is uncertain. While it has taken Dr. Gilbert over a decade to get these drugs to this point it could be as little as five years before these treatments are available to patients. All that’s required is financial support.
WORLD-LEADING STUDIES TO MAKE DIAGNOSIS EASY, PAINLESS AND FAST
Dr. Darren Yuen is a nephrologist, a scientist with the hospital’s Keenan Research Centre for Biomedical Science, and a co-founder of Fibrocor along with Dr. Gilbert.
Along with his team, he conducted the world’s largest clinical trial in kidney scarring using MRI technology. While the current gold-standard diagnostic test for kidney scarring is a painful needle biopsy that can cause internal bleeding and extracts only a tiny sample, this new MRI test is painless, safe and can assess the entire kidney. It allows experts to diagnose the extent of scarring and predict the future health of kidneys in transplant patients. The safety and effectiveness of this procedure have proven so sound it has already changed how St. Michael’s Transplant program provides care. Now all transplant patients requiring a biopsy at our centre are screened via MRI.
Next up is a world-first clinical trial of the MRI test in all patients with kidney disease.
But MRI machines are not available at all hospitals and clinics. So Dr. Yuen has also developed new ultrasound technology that can measure kidney scarring. Animal modeling of this ultrasound test is complete and a framework for a clinical trial is ready to be deployed. Using ultrasound to assess kidney function is cheaper and more widely available. The end goal is an ultrasound in a physician’s office rather than at a specialized imaging clinic so patients can get answers faster.
KIDNEY DISEASE BIOBANK
Despite the remarkable progress made so far, our researchers want to develop more tests and treatments. That requires human tissue.
Obtaining it is normally a serious challenge. Not at St. Michael’s. In collaboration with Dr. Jeff Wrana, a senior investigator at the Lunenfeld-Tanenbaum Research Institute, Dr. Gilbert and Dr. Yuen have developed a program that marries clinical patient data from our Transplant and Kidney Care Centre with the gene information they’ve extracted from preserved tissue samples. They then compared a list of 14,000 genes related to kidney scarring with a patient’s disease progression, allowing the scientists to determine the genes that predict a rapid decline in kidney function. These studies have already led to the identification of new ways to treat kidney scarring.
This program is only possible because St. Michael’s has a unique way of thinking and working: collaboratively. Our pathology department allows unfettered access to perfectly preserved human tissue, going back 15 years. Dr. Gilbert points out that “this kind of collaboration just doesn’t exist elsewhere. Other people around the world are trying to use fresh tissue and it’s going to take them 10-15 years to catch up. We can use archival material that’s sitting in the cupboard.”
St. Michael’s is at the forefront of discovery when it comes to kidney disease and our scientists have the potential to profoundly change the lives of patients everywhere.
Please join us in supporting the transformational work of the Scar Wars project.
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