Researchers at the Uniformed Services University for the Health Sciences (USU) and HJF have developed small molecules that can be used to reactivate embryonic and fetal hemoglobin expression for use as therapeutics for sickle-cell disease (SCD) and β-Thalassemia.

Applications and Advantages

• Effective inducing of embryonic and fetal hemoglobin expression as potential curative treatment of SCD and β-Thalassemia
• Current treatment methods focused on pain relief; blood transfusions or bone-marrow transplants are repetitive, expensive, or not easily accessible

Innovation Description

SCD and β-thalassemia are the most common monogenic disorders worldwide. SCD results from synthesis of abnormal hemoglobin while with β-Thalassemia there is reduced expression or absence of β-globins. Current treatment options include repeated pain management, blood transfusions or bone marrow transplant- which are cumbersome, non-curative, expensive, or a combination thereof.

Researchers at USU and HJF found that inhibiting activities of SETBP1 (a transcription factor) or XPO1 (a nuclear export protein) can activate transcription of embryonic and fetal hemoglobin genes, thus providing methods for treating hemoglobinopathy including sickle cell disease (SCD) and β-thalassemia. Two families of SETBP1 small molecule inhibitors as well as a list of XPO1 inhibitors that demonstrate potent activation of embryonic and fetal hemoglobin expressions in vitro are presented.

Fig 1. Disclosed small molecules increased
embryonic hemoglobin expression levels in
Murine Erythroleukemia cells

Inventors

• Yang Du, Ph.D., USU
• Nhu Nguyen, Ph.D., HJF,
• Kristbjorn Gudmundsson, Ph.D., HJF

Innovation Status

Two sets of small molecules have been shown to demonstrate potent activation of embryonic and fetal hemoglobin expressions in vitro.

Intellectual Property Status

A patent application has been filed in the United States (17/616,158)