It is estimated that one person in forty to sixty thousand is affected by Fabry disease. Approximately five hundred Canadians are known to have Fabry disease.
The pilot study is the first in the world to successfully treat Fabry disease patients using gene therapy.
Jeffrey Medin, M.D. of the Wisconsin Medical College, led the project. Dr. Medin commented that after working on the treatment for twenty years to now see that the treatment is effective is extremely gratifying. He said the scientists were “elated”.
About Fabry Disease
Alpha-galactosidase-A deficiency (Fabry disease) results from low levels of enzymes or faulty enzymes that are required to metabolize lipids. Lipids are fatty substances such as waxes, oils, or fatty acids.
Fabry disease patients are affected by a poorly functioning GLA gene. Their system cannot produce the proper type of enzyme needed to break down fat. The malfunctioning gene causes an accumulation of fat that can result in damage to the heart and brain. In addition, patients experience gastrointestinal issues. The kidneys are also affected leading to renal failure.
Symptoms, which generally surface during childhood, may include burning sensations in the patient’s legs and arms that increase during exercise or hot weather.
About the Treatment
The treatment involved collecting the blood stem cells from the Fabry patient. Then copies of the patient’s normal genes were injected into the blood stem cells using an engineered virus. At that point, the engineered cells were reinfused into the patient.
The current treatment requires infusions of enzymes at two-week intervals. The new gene therapy only requires one treatment. That treatment may prove more effective based on the fact that the engineered stem cells offer continuous production of the newly-corrected forms of defective enzymes.
Five male patients participated in the study. The pilot study was conducted at the Foothills Medical Center in Calgary, Alberta, Toronto’s Princess Margaret Centre, and Halifax at the Queen Elizabeth II Center.
About the Study Results
Within a week, the five patients who received gene therapy were producing a corrected form of the enzyme that rose to almost normal levels.
Based on the positive results of the study, Health Canada gave its approval to all five patients to discontinue their current enzyme therapy. Three of the five patients in the study agreed to stop their therapy.
The follow-up period ran from January 2017 through February 2020 with an extended period to February 2024.
About the First Patient
On January 11, 2017, 52-year-old Darren Bidulka became the first Fabry disease patient to receive treatment. Darren had been receiving enzyme therapy every two weeks since his diagnosis in 2005. The treatment was administered at the Foothills Medical Centre in Alberta, Canada.
The results for Darren and the other four participants showed that with one injection of the gene therapy their enzyme levels were restored. Their levels were no longer considered to be deficient.
Now the next test for the treatment is to see whether the single dose will continue to be effective in the long term. However, patients are experiencing positive effects several years after the conclusion of their treatment.
Health Canada approved the modified lentivirus for use in experimental trials. This is the first time it has been used in gene therapy. The virus was rendered harmless and expanded with a gene normally associated with the missing enzyme.
The lentivirus and other similar viruses are responsible for causing AIDS and other such disorders. They are used universally in clinical trials because they can easily insert genetic substances into cells. Lentiviruses are also easy to manufacture in large quantities.
Men are More Affected
The Fabry disease gene is inherited as an X-linked disorder. Therefore, males are affected in larger numbers than females and experience shorter lives and many more symptoms.
The symptoms may include kidney failure, burning feet and/or hands, or various gastrointestinal symptoms. These symptoms include frequent bowel movements, abdominal cramping, diarrhea, vomiting, and nausea.
If left untreated, males have a lifespan of fifty-eight years. Females’ lifespan may extend to seventy-five years.
The participating researchers acknowledge that it may take several years of continued testing before the treatment is accepted as a standard of care.