Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Hematology

Thalassemia; sickle cell disease

Lysine-specific histone demethylase 1
(KDM1A; LSD1)

In vitro and mouse studies suggest inhibiting LSD1 could help treat sickle cell disease and b-thalassemia. Inducing hemoglobin-g A (HBG1) expression reduces symptoms of b-globinopathies including b-thalassemia and sickle cell disease, but current inducers have limited efficacy and can cause toxicity. In transgenic mice expressing human hemoglobin-b (HBB) to model the diseases, inhibition of the HBG1 transcriptional repressor LSD1 with tranylcypromine increased HBG1 expression compared with no inhibition. Next steps could include testing LSD1 inhibition in additional models.
Tranylcypromine is a generic monoamine oxidase inhibitor (MAOI) marketed to treat depression.
Oryzon Genomics S.A.'s LSD1 inhibitor, ORY-1001, is in Phase I/II testing to treat acute myelogenous leukemia (AML).

SciBX 6(8); doi:10.1038/scibx.2013.196
Published online Feb. 28, 2013

Patent and licensing status unavailable

Shi, L. et al. Nat. Med.; published online Feb. 17, 2013;
doi:10.1038/nm.3101
Contact: Osamu Tanabe, University of Michigan Medical School, Ann Arbor, Michigan
e-mail:
otanabe@umich.edu

Contact: James D. Engel, same affiliation as above
e-mail:
engel@umich.edu