The patient whose chronic granulomatous disease (CGD) was treated in a world first last year at CHU Sainte-Justine can essentially be considered “cured,” says the doctor who supervised his treatment in Montreal.
Last spring, Dr. Élie Haddad and his colleagues used a gene therapy called “prime editing” to correct, directly in the patient’s hematopoietic stem cells, the genetic mutation responsible for this serious immune system disease.
And even though great caution must always be exercised before declaring a cure in connection with such a sophisticated therapy, for which there is little historical data, it is difficult, one year later, not to tell the patient that he is “cured,” admitted Dr. Haddad.
“It’s as if, even though we believe deep down that there is a strong chance he is cured, we refuse to give him the good news and instead leave him with a sword of Damocles hanging over his head,” said the researcher, whose enthusiasm is palpable even over the phone.
That being said, at this time, the 18-year-old patient shows “no symptoms whatsoever,” about three-quarters of the diseased white blood cells have been corrected (“it’s stable, it’s exactly what we had at the beginning”) and “this stability strongly suggests that it will last forever, so it’s perfect, we’re very, very happy and he has a normal life,” applauded Dr. Haddad.
In a recent update published by the prestigious New England Journal of Medicine, Dr. Haddad’s team also reported extremely encouraging data for a second patient who benefited from 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,” they write.
Even though he lives in British Columbia, and even though everything that can be delegated to Vancouver is, the young patient continues to visit CHU Sainte-Justine regularly so that researchers can keep an eye on how things are progressing.
“We monitor it like milk on the stove to make sure we don’t miss anything,” said Dr. Haddad, who is the principal investigator for the clinical trial at Sainte-Justine University Hospital Center and a professor at the Université de Montreal’s Faculty of Medicine. The best sign is when the patient gets tired of coming in. If they feel like they’re coming in for nothing, that means they’re on the road to recovery.”
The usual treatment for CGD is similar to that used for certain types of leukemia: the patient’s bone marrow—where the immune system’s white blood cells are formed—is destroyed with very aggressive chemotherapy, and then healthy bone marrow from a donor is transplanted.
However, this is a very painful treatment for the patient and carries several risks, such as the body rejecting the transplant.
The “prime editing” technique avoids some of these problems. First, the preparatory chemotherapy, while still unpleasant, is a little less “brutal” for the patient. Subsequently, since it is the patient’s own hematopoietic cells that are returned to them after gene editing in the laboratory, rejection is not possible. The survival rate should therefore, in theory, increase from 80 per cent or 90 per cent to 100 per cent.
Gene therapy as we knew it until now, Dr. Haddad explained last year, consisted of replacing a defective gene with a new healthy gene.
Prime editing takes this to the next level and makes it possible to correct virtually any mutation, said Dr. Haddad, who uses expressions such as “revolution,” “magic wand,” “absolutely brilliant,” and “completely crazy” when discussing the technique.
And this is probably just the beginning: from genetic diseases present at birth to genetic mutations acquired along the way, such as cancer, we have yet to see the full potential of prime editing, he predicted.
“A success like this shows that we are capable of correcting a genetic abnormality,” concluded Dr. Haddad. “And given the number of absolutely incredible diseases that depend on a genetic mutation, it opens the door to correcting many other diseases, at least conceptually. (…) We’re no longer selling a dream, we’re selling reality.”
–This report by La Presse Canadienne was translated by CityNews
