MONTREAL — A patient with chronic granulomatous disease (CGD) who received a groundbreaking gene therapy at Sainte-Justine University Hospital Center last year is now considered “cured,” according to the physician who oversaw his treatment.
Dr. Élie Haddad and his team utilized a gene therapy technique called “prime editing” last spring to correct the genetic mutation responsible for this severe immune system disorder directly within the patient’s hematopoietic stem cells. CGD is a rare inherited condition that impairs the body’s ability to fight infections.
While caution is always warranted when discussing a cure following such a sophisticated therapy with limited long-term data, Dr. Haddad admitted it’s difficult, a year later, not to deliver the positive news to the patient. “It’s as if we’ve been holding back on giving him good news, keeping a Damocles’ sword hanging over his head,” he said, his enthusiasm evident.
Currently, the 18-year-classic patient shows “no symptoms of anything,” with approximately three-quarters of the affected white blood cells now corrected – a state that remains “stable, exactly as we saw initially.” This stability, Dr. Haddad explained, “strongly suggests it will last, which is perfect. We are very pleased and he is living a normal life.”
Recent updates published in the prestigious New England Journal of Medicine also report highly encouraging data for a second patient who underwent the same therapy.
“These results demonstrate that ‘prime editing’ can achieve high levels of precise correction and, combined with clinical data, support the development of this approach as a therapeutic platform for CGD and other genetic diseases,” the team wrote.
Although the patient now resides in British Columbia, he continues to visit Sainte-Justine regularly to allow researchers to monitor his progress. “We’re watching him closely to ensure we don’t miss anything,” Dr. Haddad said, who is the principal investigator of the clinical trial at Sainte-Justine and a professor at the University of Montreal’s Faculty of Medicine. “The best sign is when the patient gets tired of coming – if he feels his visits are unnecessary, that means he’s on the path to recovery.”
From Dream to Reality
Traditional CGD treatment mirrors those used for certain leukemias: the patient’s bone marrow – where immune system white blood cells are formed – is destroyed with aggressive chemotherapy, followed by a bone marrow transplant from a healthy donor.
This process is arduous for patients and carries risks, including the possibility of the body rejecting the transplant.
The “prime editing” technique aims to mitigate some of these challenges. While the preparatory chemotherapy isn’t effortless, it’s less “brutal” than traditional methods. Since the patient receives their own genetically edited hematopoietic cells, there’s no risk of rejection, potentially raising the survival rate from 80% or 90% to 100%.
Previously, gene therapy involved replacing a defective gene with a healthy one, Dr. Haddad explained last year. Prime editing takes it a step further, allowing for the correction of virtually any mutation. Dr. Haddad described the technique with terms like “revolution,” “magic wand,” “absolutely brilliant,” and “completely crazy.”
Here’s likely just the beginning: from genetic diseases present at birth to acquired mutations like cancer, the potential of “prime editing” is still unfolding, he predicted.
“A success like this demonstrates our ability to correct a genetic anomaly,” Dr. Haddad concluded. “Given the number of incredible diseases dependent on a genetic mutation, it opens the door to correcting many others, at least conceptually. (…) We’re no longer selling a dream, we’re selling reality.”
