Calgary researchers are working to find a cure for a rare enzyme deficiency and are taking part in the first gene therapy clinical trial in the world for Fabry disease.

A gene called GLA changes in people with Fabry disease and it can’t make enough enzyme to break down a fatty substance called Gb3. When Gb3 builds up in the body it can lead to problems in the kidneys, heart and brain.

Fabry disease can shorten the lifespan of people who have it by as much as 40 years and about 400 Canadians, including 25 Calgarians, are affected by the disease.

Promising gene therapy results in mice performed in the laboratory of Dr. Jeffrey Medin at the University Health Network in Toronto prompted the clinical trial.

The project is headquartered in Toronto but doctors and scientists in Calgary will play a major role in the trial as will the lab at the Foothills Medical Centre which has specialized expertise in the stem cell filtering process.

“The trigger that’s making all this possible is Calgary’s expertise in isolating the specific blood stem cells we need,” says Dr. Medin. “Without a sufficient quantity of those stem cells to work with, our likelihood of success would be greatly reduced.”

The study will be the first in the country to test a gene therapy for an inherited metabolic disorder.

Here’s how it works:

  • Researchers first remove a quantity of stem cells from a Fabry patient’s blood
  • Then a working copy of a new gene will be inserted into the stem cells using a specially engineered virus
  • During the final phase of the trial, researchers hope to transplant these stem cells back into the donor patient and the new, working copy of the gene will make the missing enzyme.

“We hope this will one day become a form of treatment that effectively cures Fabry disease,” says Dr. Aneal Khan, a medical geneticist based at Alberta Children’s Hospital, who is leading the Calgary segment of the national project.

Calgarian Christopher Armstrong, 34, was diagnosed in 2007 with Fabry disease and recently donated his blood for key initial experiments for the first phase of the trial.

Nearly a billion of Armstrong’s CD34+ cells were isolated and will be sent to the lab in Toronto

Researchers will take those cells and, using a modified virus, insert a working copy of the GLA gene into the stem cells.

“We use a type of virus called a lentivirus, which has been modified in a couple of critical ways,” says Dr. Medin, who is also a professor in the Department of Medical Biophysics at the University of Toronto. “First, it’s been stripped of any of its disease-causing capability and is safe. Second, it has the corrected functional GLA gene, which will cause the donor cells to make the correct enzyme. When the corrected cells circulate in the blood, they also secrete the enzyme, which is then taken up by unmodified cells. This effectively extends the therapy afforded by the modified stem cells.”

Armstrong is currently on Enzyme Replacement Therapy (ERT), which requires a home care nurse to come to his house every two weeks to administer medication.

The infusions help manage his illness but they aren’t a cure.

Armstrong has experienced a thickening in one of the walls of his heart due to Fabry disease. “Even if the research meant that I had to come in once every six months for Enzyme Replacement Therapy, instead of every two weeks, then it would still be another step toward living a normal life,” Armstrong says.

The team hopes to treat the first human Fabry disease patient after several phases of the trial are complete and the pre-clinical experimental results have satisfied the regulatory requirements of Health Canada.

They estimate that will happen within two years.