New clinical trial unit performs Canada's first gene therapy for urea cycle disorder

A joint University of Calgary Cumming School of Medicine (CSM) and Alberta Health Services (AHS) initiative is offering new hope to those with a serious illness thanks to groundbreaking research in the new Clinical Trials Unit (CTU) at the Foothills Medical Centre (FMC).

The CTU’s inaugural study participant, 30-year-old Josh McQuillin from Prince George, B.C., is the first Canadian in history to receive a direct intravenous injection gene replacement therapy to treat urea cycle disorder, a rare genetic disease. Only three other people in the world have undergone similar gene therapy treatment. 

“I lived a normal life up until I was 12 and then got really, really sick. The doctors had no idea what was wrong with me but they say I almost died,” he says.

McQuillin was diagnosed with a urea cycle disorder (UCD), a genetic disease causing ammonia to build up in the body that can lead to brain damage or death. Ammonia is naturally produced as the body metabolizes protein, but for those with a UCD, the process of converting ammonia to urea (the harmless substance giving urine its yellow colour) does not work properly.

The condition required McQuillin to take up to 36 pills a day, adhere to a strict diet and limit travel and activities so he was always close to a hospital. Simple things like missing a meal or eating too much protein could result in a life-threatening situation requiring lengthy hospital stays. 

McQuillin received experimental gene replacement therapy at the CTU that gave him a working copy of the gene directly into his liver from an intravenous injection. His liver can now process ammonia effectively, giving McQuillin a new lease on life.

“It’s like night and day,” he says. “My exercise has changed, my sleep patterns have changed, my diet has changed — it’s really incredible.”

New treatment options due to research

Dr. Aneal Khan, MD, the study lead and associate professor in the departments of medical genetics and paediatrics and pictured with McQuillin above, says gene therapy holds tremendous promise as an effective treatment for a number of disorders, offering significant benefits to patients and the health-care system.

“With gene therapy we use modified viruses to add new genes to a patient's cells so that they have a working copy of the gene,” says Khan, who is also a member of the CSM’s Alberta Children’s Hospital Research Institute. “This is highly personalized, precision medicine that can drastically improve the quality of life for people born with a genetic abnormality.”

Khan adds many patients with genetic disorders like McQuillin must take expensive medications every day for the rest of their lives and require frequent hospitalization with numerous complications. The estimated cost of treating UCD is about $1 million per year per patient

The CTU is a self-sustaining entity funded through research programs with industry and government sponsors.

It is unique in that it’s housed in the Foothills Medical Centre’s intensive care unit (ICU), and managed by the hospital’s critical care team.  This allows patients with rare or serious disorders who may require immediate medical attention to safely participate in research. 

Dr. Christopher (Chip) Doig, MD, a medical director in intensive care for Alberta Health Services’ Calgary Zone, says the CTU is powerful example of how academic and clinical partnerships open up new options for patients and opportunities for researchers to investigate new therapies for a broad spectrum of disorders.

“As a hospital ICU, we’re not going out and actively looking for studies,” he says. “What we are doing is making the opportunities available to world-class researchers like Dr. Khan and his team to benefit patients. Although the CTU is new, many researchers in a number of areas have expressed interest and excitement about its potential. Our hope is to see more trials that could involve gene therapy and personalized medicine in everything from cardiac disease to cancer.”

From idea to implementation

Dr. Mark Swain, MD, a liver specialist and clinician scientist is already thinking about research studies involving new therapies that could help his patients. Swain, a member of the Snyder Institute for Chronic Disease, first proposed a phase one trial clinic (now the CTU) about five years ago, to leverage the expertise at the university and FMC. He reached out to number of colleagues including Dr. Derek Exner, MD, associate dean of research, clinical trials, at CSM and Dr. Peter Jamieson, MD, Foothills Medical Centre medical director

“A phase one trial is the first time a treatment is being tested in humans. There are many unknowns, we need to determine the best dosage, and identify associated side-effects,” says Exner, a professor in the departments of cardiac sciences, medicine, and community health services at CSM and a member of Libin Cardiovascular Institute of Alberta and the O’Brien Institute for Public Health. “Having ready access to highly trained nursing support and an on-site physician trained in acute care clinical support really expands our ability to offer new therapies to people who aren’t responding to traditional treatments.”  

Following renovations, the research pharmacy at the university received biohazard level two status, which allows the pharmacy to prepare and store viral vector-based drugs, like the modified virus used to treat McQuillan.   

A new lease on life

Following the treatment, McQuillin is off his medication and no longer needs to think about what or when he has to eat, or where he can go to ensure a hospital is nearby.

“I was told not to travel to the developing world because I couldn’t be sure I’d get the treatment I’d need if I got sick,” he says. “Even camping for a couple days was an issue because I might be too far from a hospital.

“Now I can do whatever I want without worrying about maybe I’ll feel okay, or maybe I won’t. I feel like I’m back to normal.” 

Steering committee reviews research applications

A steering committee which includes representatives from UCalgary and AHS has been formed to review research applications for the Clinical Trials Unit. The committee is looking for studies that will make significant medical breakthroughs or offer innovative options to patients with a rare disease or serious ongoing illness.

If you would like to submit a research study for consideration, please contact Sabine Moritz at Heritage Medical Research Clinic sabine.moritz@ucalgary.ca (403) 220-8754.

Alberta Health Services is the provincial health authority responsible for planning and delivering health supports and services for more than four million adults and children living in Alberta. Its mission is to provide a patient-focused, quality health system that is accessible and sustainable for all Albertans.

The University of Calgary’s Cumming School of Medicine is a leader in health research, with an international reputation for excellence and innovation in health-care research and education. On June 17, 2014, the University Of Calgary Faculty of Medicine was formally named the Cumming School of Medicine in recognition of Geoffrey Cumming’s generous gift to the university.

In addition to his position with Alberta Health Services, Dr. Chip Doig, MD, is a professor in the departments of Critical Care Medicine, Community Health Services, and Medicine at the CSM and a member of the Snyder Institute for Chronic Disease, and the O’Brien Institute for Public Health.