Research on gene therapy for rare inherited disease reduces costly, regular treatment

A researcher says the experimental use of gene therapy for a rare inherited disorder is saving almost as much money for treatment of five patients as the study itself costs.

The early-stage study published last year found that three of the men being treated for Fabry disease were able to stop using enzyme-replacement therapy — which costs about $300,000 annually — once they started on the "one-time" gene therapy.

Dr. Michael West, a co-author and kidney specialist in Halifax, says the overall savings have been $3.7 million, against research costs to date of about $4 million — which was largely provided by the federal Canadian Institutes of Health Research.

Fabry disease is a rare disorder that leaves the body unable to produce the correct version of an enzyme that breaks down fatty materials — leading to major damage to vital organs and shortened lifespans. Some people suffer various symptoms including pain in their hands and feet, intestinal problems and chronic fatigue.

Ryan Deveau of Dartmouth was one of five men to participate in the study.

He has been receiving the standard treatment for close to 20 years, dedicating a few hours every two weeks to get an infusion of enzymes. 

He says while this treatment has worked well for him, he wanted to get involved with this study because future generations of people with Fabry disease could benefit from it. 

"I always like to be part of these things because if people don't say yes, none of these trials would ever get off the ground," said Deveau, 44. "These are the things that will make future generations not have to worry about Fabry disease and, eventually, hopefully, not worry about it at all."

He said he went without his infusions for five years after being part of the genetic experiment, which saved him hours of his time, and also saved the government money.

Stem cells

The gene therapy uses the stem cells taken from the men's bone marrow to deliver a replacement copy of the faulty gene.

The research team wrote in the Journal of Clinical and Translational Medicine last year that one of the men with advanced kidney disease saw his condition stabilize, and the researchers also found that none of the men had major events such as heart attacks or kidney failure caused by Fabry over the last five years, West said.

"These patients are still producing more of the needed enzymes than they did prior to the gene therapy," said the 72-year-old physician, who works at the Queen Elizabeth II Health Sciences Centre in Halifax and is a professor at Dalhousie University.

West said in other instances of gene therapy there's been instances of severe side effects from procedures, including the development of various forms of cancer.

However, West said since the men received their gene therapy for Fabry between 2016 and 2018, there has been just two instances of side effects, neither of which were a direct result of the therapy itself.

Rather, in one case, a chemotherapy drug used to "make space" in bone marrow for grafting in modified cells caused a man's white blood cell count to fall. He was treated with antibiotics for a potential infection and recovered, West said.

In a second case, a man developed a large bruise in his leg, which the researchers believe was due to possible side effects of the chemotherapy drug.

Worth the effort

West said while the research needs to go to larger-scale studies before it becomes conventional treatment, he believes it's worth pursuing due in part to the costs and "the burden to patients" of the existing therapy.

The specialist said that conventional enzyme-replacement therapy has to occur every two weeks, requiring approximately two hours for each treatment.

Out of the roughly 540 people with Fabry in Canada, the researcher says about 100 are in Nova Scotia.

It's believed the first person with the genetic mutation can be traced back to a French woman who immigrated to Lunenburg, N.S., in the colonial era, and her descendants carried the faulty gene through 18 generations that followed.

"Currently, there's some cases in Ontario, there's some in British Columbia, there's some in the U.K., some cases in Florida, but they all originated from here and they share the same mutation," West said.

Cost unknown

West said the ultimate cost of gene therapy per patient has yet to be determined, as it first would have to be approved by the major regulatory agencies as an accepted treatment.

But he said one option for inherited genetic diseases, where there is a relatively small group of patients, would be for government research agencies to develop and own the treatment themselves, and then earn fees to provide the treatments to other national health systems.

West said he realizes the sample size is small, and the goal is now to create a similar study with 25 to 30 patients, including women, over a two- to three-year period.