New gene therapy may reduce bleeding risk for haemophilia patients

A research team led by researchers of Indian descent has developed a breakthrough single-injection gene therapy 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 protein factor IX (FIX), which is needed to form blood clots that help prevent or stop bleeding.

The gene responsible for the production of the FIX protein is located on the X chromosome, so the severe form of hemophilia B is significantly more common in men.

Currently, hemophilia B patients must inject themselves regularly—usually weekly—with recombinant FIX, regular replacement therapy, to prevent excessive bleeding. Despite advances in treatment, patients may continue to see debilitating joint damage.

But a new type of adeno-associated virus (AAV) gene therapy candidate called FLT180a, developed by University College London researchers, treats severe and moderate cases of the disease.

The study, published in the New England Journal of Medicine, showed that single treatment with FLT180a resulted in sustained hepatic production of the FIX protein in nine out of ten patients at four different dose levels, eliminating the need for regular replacement therapy.

“Eliminating the need for hemophilia patients to regularly inject missing proteins is an important step towards improving their quality of life,” said lead author Professor Pratima Choudary, Royal Free Hospital at UCL Cancer Institute.

AAV gene therapy works by using packaging proteins, which are found in the outer layer of the virus, to deliver copies of functioning genes directly to the patient’s tissues to compensate for genes that are not functioning properly.

The newly synthesized protein is released into the blood, and a single infusion can produce long-lasting effects.

Patients must take immunosuppressive drugs for several weeks to several months to prevent their immune system from resisting therapy.

While treatment was generally well tolerated, all patients experienced some form of adverse reaction, with abnormal blood clots in patients receiving the highest dose of FLT180a and having the highest levels of FIX protein.

In nine out of ten patients, the treatment resulted in a sustained increase in FIX protein production, leading to a reduction in excessive bleeding. They also no longer need weekly FIX protein injections.

After 26 weeks, five patients had normal FIX protein levels, three had low but elevated levels, and one patient treated with the highest dose had very high levels.

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