Research highlight

An RNA therapeutic for hemophilia

Nature Medicine

April 14, 2015

A therapeutic RNA that reduces levels of a protein that inhibits blood clotting is effective in mouse and non-human primate models of hemophilia, reports a study published this week in Nature Medicine. This agent is currently being tested in a Phase 1 clinical trial.

Hemophilia is caused by mutations that affect the body's ability to control bleeding due to a lack of the blood clotting proteins factor VIII or factor IX. However, mutations that disable other proteins that inhibit blood clotting can counteract the effects of factor VIII or factor IX mutations.

Akin Akinc and colleagues designed an RNA interference therapeutic, ALN-AT3, to target one of these anti-clotting proteins, antithrombin, which inhibits thrombin, a key clotting protein. ALN-AT3 treatment increased blood clotting in 17 mice lacking factor VIII due to a genetic mutation and increased thrombin generation in four long-tailed macaques injected with an antibody that targets factor VIII.

Current treatment of hemophilia relies on injection of recombinant factor VIII or factor IX protein. The finding that ALN-AT3 is effective in the presence of anti-factor VIII antibodies suggests that it may be beneficial in patients who develop such antibodies and thereby become resistant to factor replacement therapy.

doi: 10.1038/nm.3847

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