Use of Ulk1 modulators to treat thalassemia (SJ-18-0004)

St. Jude Reference #SJ-18-0004


Buildup of free alpha globin is a major determinant of the pathophysiology of beta thalassemia. Beta thalassemia is a common genetic anemia caused by mutations in the HBB gene, which encodes the beta globin subunit of hemoglobin.  This results in the accumulation of free alpha globin which forms precipitates that damage and kill red blood cells and their precursors.

Researchers at St. Jude used a mouse model for beta thalassemia to show for the first time, that the Ulk kinase gene, which encodes a protein that drives some forms of autophagy, participates in removal of excess free alpha globin; showing that genetic ablation of Ulk1 in beta thalassemic mice results in increased accumulation of free alpha globin and exacerbation of the anemia phenotypes. The kinase activity of Ulk can be activated by numerous drugs, including some that are FDA approved such as metformin and rapamycin. By activating Ulk with drugs, the researchers are testing if it may be possible to treat some forms of thalassemia.

This discovery can lead to new unanticipated treatments for some forms of beta thalassemia using already approved drugs and compounds that are in clinical development for other diseases.  That is, a new application for old and new drugs.  Inhibition of Ulk1 will likely not cure the most severe forms of beta thalassemia; however, it might work for “thalassemia intermedia”, which affects many millions worldwide using safe drugs that are already approved.


alpha globin, beta thalassemia, HBB gene, hemoglobin, Ulk kinase,  gene

Granted patents or published applications

International patent application WO 2019/084402 A1 (published)

Related scientific references

Abstract submitted for review to ASH.

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