Clinical Pilot Study of Autologous Stem Cell Transplantation of CD34+ Cells Engineered to Express α-Galactosidase A in Patients with Fabry Disease Identifier: NCT02800070

Fabry disease is a genetic disease that results from the build-up of a particular type of fat, called globotriaosylceramide (GB3) in the body. Patients with Fabry disease can have features that include chronic pain, heart disease, kidney disease, and stroke. Fabry disease is caused by mutations in a gene called GLA. This gene provides instructions for making an enzyme called α-galactosidase A. Alpha-galactosidase A normally breaks down GB3. A change in the gene can lead to the enzyme working less effectively. As a result, GB3 builds up in cells throughout the body, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of this substance damages cells, leading to the varied signs and symptoms of Fabry disease.


There is no cure for Fabry disease. Patients with Fabry disease who do not receive any treatment are known, on average, to have a lower life expectancy. A patient with Fabry disease is born with the gene causing Fabry disease and there has been no way to repair the gene. The use of  enzyme replacement therapy (giving manufactured enzyme) has not been shown to increase life expectancy but may slow the rate of damage to organs. Enzyme replacement therapy though is not a cure for Fabry disease and many patients continue to get worsening of their symptoms despite using ERT. Enzyme replacement therapy is an infusion through an intravenous (a needle is inserted into the veins) every 2 weeks. This is designed to increase blood levels of the enzyme closer to those levels in healthy individuals. When ERT is stopped, the blood levels of the enzyme return back to the lower level seen in patients with Fabry disease and the disease will continue to advance as it would if ERT was not being used. Therefore, the only way to increase blood levels of enzyme is to get infusions of ERT for life.


Another way to increase levels of the enzyme α-galactosidase A in the blood would be to have a working copy of the GLA gene.  Researchers have been able to transfer the working copy of the GLA gene into animals and show that enzyme levels in the blood increase. Researchers have also been able to transfer a working copy of the GLA gene into human stem cells (called CD34+ cells) that have been filtered from the blood of patients with Fabry disease. When these cells were injected into mice with Fabry disease, they resulted in an increased level of the enzyme in the blood similar to that in mice that did not have Fabry disease.   If these CD34+ stem cells with a working copy of the GLA could be inserted into patients with Fabry disease, this could be a method to produce continuously higher levels of enzyme and this may be a better form of treatment in the long run.


The FACTS study is the first human phase I gene therapy trial and has been approved by Health Canada and Research Ethics Boards at the University of Calgary, Dalhousie University and the University of Toronto.  Hospitals at each of these centres in Canada are eligible to try to treat patients as part of a clinical trial.  The procedure involves the following steps:

1. Patients with Fabry disease who fulfill inclusion criteria and do not have any of the exclusion criteria, who have health care in Canada, who reside in a province with a recruitment centre and who are already on enzyme replacement therapy are eligible to be part of the study.

2. Patients undergo a series of tests in the initial phase to test for suitability and safety to be able to undergo the procedures in the trial.

3. The next phase is designed to collect as many (CD34+) stem cells as possible.  Enough stem cells must be collected to do the gene transfer and, in case it’s needed, a “back-up” collection of stem cells is also collected.  In order to get this many stem cells, the body’s production of (CD34+) stem cells must be enhanced using a substance called GCSF which is injected twice a day for up to 5 days.  This causes the level of stem cells to increase substantially in the blood.  An intravenous line is inserted and blood is “filtered” to collect just the stem cells while the remainder of the blood components are returned back to the patient.  The procedure, called leukapheresis, is performed while the patient is awake and does not cause pain.

4. The stem cells are then shipped to the Juravinski Cancer Centre in Hamilton, Ontario.  There, additional sorting is carried out so that just (CD34+) stem cells remain.  This is like a purification step.

5. The (CD34+) stem cells are then shipped to the Philip S. Orsino Cell Therapy Facility in Toronto.  There the special lentivirus that researchers have developed is added to the stem cells and allowed to culture for 2 days.  Quality and safety data from the sample is sent to Health Canada awaiting approval to use the cells.

6. In this first case, the cells were sent back to Calgary and infused into the patient from which they were originally taken.  The patient was treated with a medication called melphalan which reduced the amount of some his own stem cells to make room for the lentiviral treated stem cells.

7. We will be monitoring the patients enzyme levels and a number of safety parameters for at least 5 years to see how well the treatment has worked.


Dr. Khan would like to thank the following individuals and agencies for their support of this project:

Metabolic Research Team:

  • Shelly Jelinski, FACTS Primary Research Coordinator
  • Connie Mohan, Research Coordinator
  • Josmar Alas, Research Assistant
  • Sheila McNaughton, Research Nurse
  • Kelsey Lehman, Research Administration
  • Shelley Carle, Research Clerk

The FACTS site team:

  • Dr. Ahsan Chaudhry, oncology, Departments of Oncology and Medicine, Cumming School of Medicine, University of Calgary
  • Dr. Andrew Daly, hematology and internal medicine, Departments of Oncology and Medicine, Cumming School of Medicine, University of Calgary
  • Dr. Peter Duggan, hematology, Departments of Oncology and Medicine, Cumming School of Medicine, University of Calgary.
  • Dr. John Klassen, internal medicine, Departments of Pathology and Laboratory Medicine, member of the Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary
  • Dr. Nicole Prokopishyn, Director, Cellular Therapy Lab, Calgary Laboratory Services, Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary
  • Robyn Casey, Emeritus Investigator
  • Alberta Health Services
  • University of Calgary
  • Calgary Laboratory Services
  • The Special Services Building lab team.

We would also like to thank the pan-Canadian FACTS team, led by the local site investigators:

  • Dr. Jeffery Medin, Principal Investigator
  • Dr. Ronan Foley in Hamilton, ON
  • Dr. Armand Keating in Toronto, ON
  • Dr. Tony Rupar in London, ON
  • Dr. Christiane Auray-Blais in Sherbrooke, QC
  • Dr. Michael West in Halifax, NS