Gene therapy shows promise taming rare disease: researcher

Fabry sufferers, who number only 500 known cases in Canada, must undergo enzyme therapy once every two weeks — akin to those tethered to kidney dialysis, said Khan

Bill Kaufmann 3 minute read February 25, 2021

From left: Dr. Jeffrey Medin, Dr. Aneal Khan and study subject Darren Bidulka during clinical trials at Foothills Medical Centre in 2017. Courtesy Darren Bidulka

A silver lining in HIV is showing promise in controlling a rare chronic disease, says a University of Calgary researcher heading up a groundbreaking study.

By extracting properties from the virus that causes AIDS, researchers have been able to craft what could be a treatment for Fabry disease, a DNA disorder that attacks organs such as the kidneys, brain and heart, said Dr. Aneal Khan of the Cumming School of Medicine.

“Even when we’re confronted with challenges from something like HIV, human ingenuity can figure out how we can get something positive from it,” said Khan.

In research that began in 2017, scientists isolated lentivirus from HIV, placing it into DNA to mimic Fabry, he said.

Lentiviruses are known for their ability to enter cells and insert genetic material.

“It merges with a patient’s DNA, then we have a working copy of a gene that produces this enzyme,” said Khan.

Those suffering from Fabry disease have a malfunctioning gene resulting in a deficiency of a certain enzyme, which leads to severe pain, diarrhea and even strokes as the disease attacks organs.

Currently, Fabry sufferers, who number only 500 known cases in Canada, must undergo enzyme therapy once every two weeks — akin to those tethered to kidney dialysis, said Khan.

“They’re tied to this treatment, they can’t take a month off and go to Mexico,” he said.

The disease also drastically lowers life expectancy, particularly in men, who typically don’t live past their 50s.

But a Phase 1 clinical trial involving five subjects — three of them in Calgary — suggests a single treatment of gene therapy boosts the production of the enzyme, possibly permanently, said Khan.

That would free them of a painful and onerous regular procedure.

“We’ve put gene into their stem cells until they make a normal or close to normal amount of enzyme,” said the researcher.

“Three of the subjects have not needed those (extra) enzymes and are producing what looks to us like adequate levels of them.”

One of those study subjects is Darren Bidulka, who was diagnosed with Fabry in 2005 and spent 13 years undergoing biweekly enzyme top-ups to control symptoms centring on his gastrointestinal system.

Without those regular enzyme treatments, the likelihood of kidney and heart failure lurked, he said.

But since a month of gene and chemotherapy in early 2017 at the Foothills Medical Centre, Bidulka has led a life untethered to those enzyme top-ups and the fear of organ failure.

“Mentally, I’m relieved I’m getting enzymes 24/7 and that my organ function is diminishing much slower,” said Bidulka, 52, whose progress is being closely monitored.

“It’s amazing — I’m grateful that for four years I haven’t had enzyme treatment, and that’s a miracle for a Fabry patient . . . maybe something can be done for someone much younger than me who won’t have to suffer any organ damage.”

A larger Phase 2 clinical trial is now underway in other countries, including Australia, while in pandemic-ridden Canada, they’ve been put on hold.

But Khan is hopeful that will build on the Phase 1 work to produce a standard therapy that’ll extend and dramatically improve the lives of Fabry sufferers like Bidulka — if not entirely cure them.

That’ll take years, but Khan said he’s looking forward to deriving satisfaction where none could be had.

“My life is giving people (bad) news, that ‘we can’t do a heck of a lot about it,’ but with this it could be ‘we’ve got this,’ ” he said.

Dr. Jeffrey Medin, who pioneered the treatment in 20 years’ work at the Princess Margaret Cancer Centre in Toronto, agreed.

“To see that patients could end up making their own enzyme and that the treatment effect was sustained is satisfying. We are elated,” he said.

BKaufmann@postmedia.com

Twitter: @BillKaufmannjrn

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