The world’s first treatment of Fabry disease with gene therapy

The results of the world’s first Canadian pilot study of patients who received gene therapy for Fabry disease show that the treatment is functioning and safe.

First used by a Canadian research team Gene therapy In 2017, we will treat patients with Fabry disease, a rare chronic disease that can damage key organs and shorten their lifespan.They report their findings in the journal today Nature Communications..

“I was one of the first people in the world to receive this treatment, and after seeing how I felt better, this is with many other Fabry patients and potentially other single gene mutation disorders. I’m definitely hoping to help patients, “says Ryan, Deveu, one of the patients in Dartmouth, Nova Scotia. “Now you don’t have to get a replacement Treatment Every two weeks, I spend more time with my family. “

Patients with Fabry disease now need to receive an injection of enzyme therapy every two weeks. Gene therapy involves receiving a single treatment that may prove clinically more effective because the modified blood stem cells continuously produce a modified version of the defective enzyme. make it possible.

“So far, gene therapy has partially or completely restored enzyme levels and is no longer considered deficient,” said Alberta Health Services clinical geneticist and member of Alberta Children’s Hospital. Dr. Anne Khan said. The Institute of Cumming Medicine, University of Calgary, leading trials in Calgary.

“These results show that a single treatment of gene therapy was sufficient to benefit patients. Now we need to see if this single dose will last for a long time. . “

Five men participated in the study and were treated at Alberta Health Services’ Foothills Medical Center in Calgary, Princess Margaret Cancer Center in Toronto, and Nova Scotia Health’s Queen Elizabeth II Health Science Center in Halifax.

As a result of gene therapy, all patients began to produce modified versions of the enzyme near normal levels within a week. Based on these initial results, all five patients were approved by Health Canada to discontinue intravenous enzyme therapy. So far, three patients have chosen to do so and are stable.

“Given that the current treatment is not a treatment, this was a truly groundbreaking study,” said Dr. Michael West, a nephrologist and collaborator at Novascosia Health, and Stephen Kuban, a hematologist. The doctor says. “This is the next step towards a better treatment and, hopefully, a treatment for this disease that can cause a lot of pain and distress to the patient. Participating patients are in the procedure. I promise to continue to benefit from the treatment years later. It’s done. “

The study will follow patients from January 2017 to February 2020, and ongoing follow-up will be extended to February 2024.

Clinicians have emphasized that years of additional testing will be required before this treatment becomes a clinically available standard treatment.

“It was humble to see that this treatment actually worked for patients,” he pioneered when he was a senior scientist at the Princess Margaret Cancer Center at the University Health Network (UHN). Dr. Jeffrey Medin says. Dr. Medin is currently a MACC Foundation professor at the University of Wisconsin Medical School and an affiliate scientist at UHN.

“After 20 years of working on this treatment, it’s satisfying to see that patients can make their own enzymes and the treatment lasts. We’re delighted!”

Darren Bidurka, 52, was the first patient to be treated at the Foothills Medical Center at Alberta Health Services on January 11, 2017. He was diagnosed with Fabry disease in 2005 and had been on enzyme therapy for many years.

“I’m really happy that this worked,” he says. “What a wonderful result, a very fascinating experience. I think this is a great success.

“We can now lead a more normal life without scheduling enzyme therapy every two weeks. This study is also very important for many patients around the world who will benefit from these discoveries. “

In this study, researchers collected large amounts of their own blood stem cells from Fabry disease patients and used a specially designed virus to inject copies of the fully functional genes involved in the enzyme into those cells. .. The modified stem cells were then transplanted back into each patient.

People with Fabry disease have a gene called GLA that does not function properly. As a result, their bodies are unable to make the correct version of the enzymes that break down fat. Its accumulation can cause problems in the kidneys, heart and brain.

Approved by Health Canada for purposes, this treatment was the first trial in Canada to use the lentivirus for gene therapy.In this case, the specially modified virus was created at the Princess Margaret Cancer Center, where the disease-causing ability was removed and reinforced with a working copy of the missing-causing gene. enzyme..

Lentivirus is a family of viruses that can cause diseases such as acquired immunodeficiency syndrome (AIDS) and is used worldwide in many clinical trials due to the ease of entry and insertion of genetic material into cells. It has been. They are well understood by the research community and are easy to mass produce for this study.

The study focused on men because the gene for Fabry disease is on the X chromosome and is inherited as an X-linked disease. Therefore, men are more affected than women. This is because each man has only one X chromosome.

Therefore, men present more Severe symptoms, Burning sensations in the limbs, renal failure, or abdominal cramps, frequent bowel movements, diarrhea, nausea, gastrointestinal symptoms such as vomiting. The average life expectancy of untreated men is 58 years and that of women is 75 years.

It is estimated that 1 in 40,000 to 60,000 people has Fabry disease. We know that more than 500 people in Canada have the disease, but we don’t know the exact number because it’s difficult to identify all the sick.

“Such research can pave the way for additional things. Clinical trial For Fabry disease and many other metabolic disorders. Several analyzes have been conducted at the University of Wisconsin Medical School, showing that it is possible to coordinate such complex studies at multiple sites across borders, “he said. Dr. Medin, who has been working on the project since he was there, says. At the National Institutes of Health in Bethesda, Maryland.