Replacing a defective gene may work better than feeding the missing protein from the outside. This is one of the results coming from a clinical trial on the efficacy of gene therapy against haemophilia A, a genetic disease caused by the lack of a blood clotting factor (factor VIII). In fact, when the body is “taught” to produce the missing protein, the bleeding episodes typical of the disease decrease and so does the need to resort to the administration of factor VIII. Hoping for the arrival, one day, of a definitive therapy for this disease.
The study of 132 severe patients
To tell the promises and the limits still to be overcome is a study published in recent days on the pages of New England Journal of Medicineshowing the results from the GENEr8-1 clinical trial, which tested the efficacy of gene therapy valoctocogene roxaparvovec in 132 patients (men, because the disease essentially affects males due to genetic characteristics) with severe haemophilia A. The therapy works in a very similar way to some already approved for other pathologies or under study: it basically makes use of a viral vector (specifically an adeno-associated vector) to ferry the genetic information necessary for production into the body. of the missing factor. A large proportion of the patients enrolled came from an observational study conducted to monitor the use of factor VIII given prophylactically (to prevent bleeding) and the recurrence of bleeding episodes. The population eligible for treatment included patients who had not developed antibodies to the vector used for gene therapy, or to factor VIII (can occur as a response to the use of drugs in the treatment of the disease) and undergoing factor VIII prophylaxis. A single infusion of gene therapy was given, while prophylactic therapy was continued for four weeks, after which it was given only as needed.
Type A haemophilia, the idea that made gene therapy more effective
by Anna Lisa Bonfranceschi
Data on valoctocogene roxaparvovec
The researchers thus observed that gene therapy increases the activity of factor VIII and reduces bleeding compared to prophylactic therapy, although – they specify – with a rather high variability both in the same patient and between different patients. Overall, after one year, approximately 88% of participants had factor VIII levels equal to or greater than 5 IU per deciliter (where IU / deciliter is a measure of factor VIII activity that is less than 1 in severe disease) and the annual use rate of factor VIII and bleeding treatments decreased by 98.6% and 83.8%, respectively. In short: 9 out of 10 patients had no bleeding to treat or had less than the prophylaxis therapy (although here too the variability was high and in some cases the bleeding also occurred after the infusion). Following some patients for up to two years, the researchers also observed a decrease in the amount of factor VIII produced over time.
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by Elisa Manacorda
The relationship between benefits and risks: more studies needed
Overall, the experts conclude, the benefit-risk profile appears favorable to the use of gene therapy, despite the need for further studies to evaluate its efficacy, durability and safety. But in practice it could represent a real change of pace for these patients, notes Courtney D. Thornburg of the University of California San Diego Health Sciences, La Jolla, in an editorial accompanying the study. For a single person, in fact, if gene therapy proves effective, it could mean giving up about 150 infusions of prophylactic therapy within a year, without risk of bleeding.
Hemophilia, less bleeding even in mild and moderate forms
