SREBP2-Targeted Therapies for treating Leukemia


This invention is a method of targeting sterol regulatory element-binding protein 2 (Srebp2) in order to treat, prevent, reverse, and/or ameliorate conditions associated with an improper number of hematopoietic stem and progenitor cells (HSPCs). Srebp2 is traditionally known as a transcription factor that plays a role in cholesterol homeostasis. However, this invention provided the first evidence that cholesterol metabolism, via the activation of Srebp2 and downstream Notch signaling, controls HSPC emergence and may be used as a therapeutic target to treat hematological disorders.


Stage of Development


In vitro data: Bioinformatics approaches using genome-wide ChIP-seq, RNA-seq, and ATAC-seq indicated that Srebp2 trans-regulates Notch pathway genes required for hematopoiesis.

In vivo data: Notch reporter zebrafish indicated that Srebp2 depletion decreased HSPCs and Srebp2 overexpression rescued HSPC emergence in these fish. Murine studies also revealed that a conserved Srebp2-dependent mechanism regulates HSPC maintenance in hypercholesterolemia.


Competitive Landscape


Hematological disorders include a broad range of diseases some of which are less debilitating and adequately controlled, and some of which present with poor prognosis and significantly reduced quality of life. Currently, drug and transfusion therapies may improve the duration and quality of life of these patients, however, these are often not curative and can even reduce the quality of life in some instances, such as in the case of leukemia patients. Additionally, bone marrow transplants may be used to replace the damaged or diseased HPSCs, however, this procedure is invasive, it is only available to a minority of patients due to the lack of available donors, and there is a risk of life-threatening complications such as infection or graft-versus-host disease.


Competitive Advantages


•       Improved quality of life

•       Tunable response (i.e. increase or decrease HSPC production according to need, different dosing regimens may facilitate more or less of a response)

•       No donor required

•       Non-invasive


Patent Information:
Licensing Contact
Paige Glumac

Longhou Fang
Qilin Gu