Scientists at Scripps Research have found an enzyme that can boost platelet production and may serve as a new approach for treating diseases of the blood including thrombocytopenia. Their findings were reported earlier this week in Proceedings of the National Academy of Sciences
"This opens up new options for treating diseases of the blood," says Paul Schimmel, PhD, professor and co-senior author of the study with Professor Zaverio Ruggeri, MD.
Previous research had shown that while the enzyme YRSACT has a crucial role in decoding DNA, 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.
Their study found that YRSACT is key to one method of platelet production. Working with a platelet-deficient mouse model, the team found that animals injected with YRSACT showed a dramatic increase in platelet production, especially under stressful conditions, such as radiation.
"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.
The researchers found that YRSACT increased 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.
To show that YRSACT could be useful in human patients, the team collaborated with a group at Kyoto University to test a stem cell line developed from a thrombocytopenia patient. 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.