Gene therapy trials led by U of C

The University of Calgary is involved in the first gene therapy trials for Fabry disease, an inherited genetic disorder. The study is led by assistant professor of genetics and pediatrics at the U of C Aneal Khan. 

These trials are the first for Fabry disease in the world and are funded by the Canada Institutes of Health Research and the Kidney Foundation of 

Fabry disease is a mutation in the GLA gene. The result is a deficiency in an enzyme that normally breaks down a lipid called GB3. Therefore, GB3 accumulates in areas such as the kidneys and heart and can cause kidney failure, strokes, heart failure and a reduced life 

During early childhood and adolescence, males with Fabry disease may experience severe pain in their hands and feet and have difficulty sweating. The diagnosis for Fabry disease is often delayed.

“It’s not a common disease. So as they go and see different specialists, the diagnosis can often be delayed by at least 10 to 15 years. Usually they are young adults by the time they get a diagnosis,” said Khan. 

There is no cure for Fabry disease. Current treatment involves injecting patients every two weeks with manufactured enzyme, which costs around $250,000 per year.

“The current standard treatment still means there is a lot of room to move forward to be able to provide them with some long-term correction,” said Khan. 

The new gene therapy treatment involves inserting working copies of the GLA gene into the stem cells obtained from clinical trial patients using a virus. Once the virus is removed, stem cells are transplanted back into the patient. 

“What we’re hoping with this treatment is to stabilize the Fabry disease so at least it doesn’t get any worse. We don’t know that we’ll be able to reverse any of the changes that are there,” said Khan. “It’s a trial to first look at safety and then we will also be looking to see if doing this allows for stable and constant production of the enzyme in the patient.”

Because the stem cells transplanted back into the patient are their own, Khan hopes that the anti-rejection medications necessarys with current treatments can be avoided. 

The study currently is in its first phase, which involves removing stem cells from Calgary patients in a process called apheresis. The stem cells are then sent to 
Toronto principal investigator Jeff Medin. The working GLA gene is then inserted into the stem cells and stem cells are injected into mice with Fabry disease.

“That would be the first attempt at correcting a human cell and then showing that it will actually correct the disease in the mouse,” said Khan.

The apheresis unit at the Foothills Medical Centre has played a major role in obtaining these stem cells from patients.

“The Calgary apheresis protocol is highly efficient so that we can get enough cells to perform an autologous transplant back into the patient whereas other protocols have struggled producing the same number of cells,” said Khan. “Without the Calgary [apheresis unit], this experiment would be very difficult to do.”

Khan expects that stem cell transplants will happen in Fabry patients in two years from now in Toronto.

“We’re hoping that after the first few transplants are done in Toronto that we are able to do the transplants here in Calgary at some point in the future as well,” said Khan.

If the study shows a response in Fabry patients, Khan hopes that other single gene diseases may be treated in a similar manner using this therapy.