A team of researchers led by people of Indian origin has developed a single gene therapy injection that can dramatically reduce the risk of bleeding in people with hemophilia B.
Hemophilia B is a rare and inherited genetic bleeding disorder caused by low levels of the factor IX (FIX) protein, which is needed to form the blood clot that helps stop or stop bleeding.
The gene responsible for making the FIX protein is located on the X chromosome, so the severe form of hemophilia B is more common in males.
Currently, patients with hemophilia B require themselves to be regularly injected – usually weekly – with recombinant FIX, that is, routine replacement therapy to stop excessive bleeding. Despite advances in treatment, patients may continue to see debilitating joint damage.
But the new type of adeno-associated virus (AAV) gene therapy candidate, called FLT180A, developed by researchers at University College London, treats severe and moderately severe cases of the condition.
The study, published in the New England Journal of Medicine, showed that a one-time treatment with FLT180a at four different dosage levels resulted in sustained production of FIX protein from the liver in nine out of 10 patients, eliminating the need for regular replacement therapy. happened.
Professor Pratima Choudhury, lead author from the Royal Free Hospital at the UCL Cancer Institute, said: “Removing the need for hemophilia patients to routinely inject themselves with the missing protein is an important step in improving their quality of life. “
AAV gene therapy works by using a packaging from a protein found in the virus’s outer coat, so that a functional copy of a gene can be delivered directly to the patient’s tissue in case one is not working properly.
Newly synthesized proteins are released into the blood and a one-time infusion can achieve long-lasting effects.
Patients need to take immunosuppressive drugs for several weeks to several months to prevent their immune system from rejecting the therapy.
While treatment was generally well tolerated, all patients experienced some form of adverse event, including abnormal blood clotting in those receiving the highest FLT180a dose and those receiving the highest levels of FIX protein.
In nine out of 10 patients, treatment resulted in a sustained increase in FIX protein production, leading to a reduction in excessive bleeding. They no longer even require weekly injections of FIX protein.
After 26 weeks, five patients had normal levels of FIX protein, three had low but increased levels, and one patient treated at the highest dose had abnormally high levels.
