Mysterious Enzyme to Stop Internal Bleeding Identified

by Colleen Fleiss on  August 16, 2018 at 8:15 AM Research News
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An enzyme that boosts platelet production and may work as a future therapeutic in thrombocytopenia condition, found Scripps Research scientists. The findings of the study are published in Proceedings of the National Academy of Sciences.
Mysterious Enzyme to Stop Internal Bleeding Identified
Mysterious Enzyme to Stop Internal Bleeding Identified

"This opens up new options for treating diseases of the blood," says Paul Schimmel, PhD, professor at Scripps Research and co-senior author of the study with Professor Zaverio Ruggeri, MD, of Scripps Research.

Previous research had shown that while the enzyme YRSACT has a crucial role in decoding DNA (a process called translation), it appears to have additional jobs in the cell. YRSACT was abundant in blood platelets, the cells that let wounds clog and heal. So, the Schimmel and Ruggeri labs sought to uncover why.

"Our animal study indicated accelerated platelet recovery, not only in antibody-induced thrombocytopenia, but also in radiation-induced thrombocytopenia," says study first author Taisuke Kanaji, PhD, MD, an institute investigator at Scripps Research.

So how does YRSACT work? The researchers found that YRSACT increases the production of large bone marrow cells called megakaryocytes, which are the precursors to platelets.

Until this discovery, thrombopoietin (TPO) was previously the only other protein known to increase platelets. Schimmel says a version of TPO is currently used as a drug to treat some cases of thrombocytopenia. However, TPO has limitations, making it unsuitable and hazardous in some clinical settings.

Showing that YRSACT could be useful in human patients posed its own challenges. Congenital thrombocytopenia is rare, and even finding the right blood cells to test in thrombocytopenia patients is like finding a needle in a haystack.

Remarkably, the Scripps researchers were able to team up with a group at the Center for iPS Cell Research and Application at Kyoto University to test a stem cell line developed from a thrombocytopenia patient.

"I think this was a beautiful collaboration of groups having distinct expertise to work together to accomplish our goal," says study co-first author Sachiko Kanaji, PhD, MD, a staff scientist at Scripps Research.

Their findings in these human cells further confirmed that YRSACT can control a mechanism in cells to produce life-saving platelets.

Taisuke Kanaji says the next step in the research is to understand the conditions-from infections to radiation-that prompt the body to activate YRSACT on its own.

Source: Eurekalert

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