The search for a cure for the most common form of hemophilia seems to have taken a giant leap forward following the striking results of a gene therapy trial in the United Kingdom.

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Could the insertion of a missing gene cure hemophilia?

A report on the trial, which is published in the New England Journal of Medicine, describes how, more than a year after receiving a single dose of gene therapy to insert a missing gene, participants with hemophilia A had normal levels of clotting factor and significant reductions in bleeding.

“We have seen mind-blowing results which have far exceeded our expectations,” notes paper co-author Prof. K. John Pasi, director of the Haemophilia Centre at Barts Health NHS Trust.

Hemophilia is an inherited disease in which the blood does not clot properly due to a defect in a gene that controls the production of a clotting factor.

The lower the level of clotting factor, the higher the chance that even the slightest injury will result in excessive bleeding, or even spontaneous internal bleeding — particularly in the joints.

Bleeding in the joints can cause progressive damage, arthritis, and pain. When the bleeding occurs in the head, it can lead to seizures and paralysis. The bleeding can be fatal if it cannot be stopped or if it takes place in the brain or another vital organ.

Hemophilia primarily affects males, and there are two main types. Hemophilia A, the most common type, results from deficiency of factor VIII, while hemophilia B results from deficiency of factor IX.

Hemophilia A is four times more common than hemophilia B and occurs in around 1 in 5,000 males. Estimates suggest that there are more than 400,000 people with hemophilia worldwide, including 20,000 in the United States and more than 2,000 in the United Kingdom, where the trial took place.

There is currently no cure for hemophilia. Effective treatments do exist, but they are expensive and involve lifelong injections several times per week to prevent bleeding.

During the gene therapy trial, 13 people with hemophilia A from across the U.K. received injections of a copy of the gene that codes for factor VIII, the blood-clotting protein that is missing in people with hemophilia A.

The participants, who were followed for up to 19 months, were treated at five hospitals: The Royal London, Guys and St Thomas’, Birmingham, Hampshire, and Cambridge.

Test results show that over 1 year after receiving their treatment, all 13 patients have been able to stop their previous treatment, and 11 are showing normal or near-normal levels of clotting factor.

“When we started out,” Prof. Pasi says, “we thought it would be a huge achievement to show a 5 percent improvement, so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is quite simply amazing.”

In a linked editorial, Dr. H. Marijke van den Berg, from the Julius Centre for Health Sciences and Primary Care at University Hospital Utrecht in the Netherlands, discusses the significance of this gene therapy trial, and also of another with hemophilia B patients.

Dr. van den Berg has quite recently observed that hemophilia is approaching an “era where clotting factor concentrates are abundant and gene therapy a reality.”

Of the new trial, she notes that while “the obtained levels are impressive, the large variation among patients needs clarification.”

One of the things that needs clarifying, explains Dr. van den Berg, is whether or not it would be possible to predict which people could receive lower doses and whether a “preconditioning regimen” might reduce the dose.

Also, because the trial excluded people whose immune systems may reject the virus used to carry the corrective gene (the AAV vector), who had no history of developing factor VIII inhibition, and who were free of hepatitis, it is not clear whether the treatment would work for most people with hemophilia A.

“Because patients who have been recruited for the current trials had to be AAV-negative, without active hepatitis, and inhibitor-negative, most patients with hemophilia cannot yet benefit from gene therapy,” notes Dr. van den Berg.

However, she suggests that if the treatment “could be perfected,” then people who are born with this disease could look forward to a “life without bleeding” and other devastating side effects.

Another important implication that Dr. van den Berg notes is that, because gene therapy may “cure” the disease with one treatment, it might make a big difference in those developing countries where people with hemophilia have no access to clotting products.

We really now have the potential to transform care for people with hemophilia using a single treatment for people who at the moment must inject themselves as often as every other day. It is so exciting.”

Prof. K. John Pasi

Read this article in Spanish.