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Selective HDAC1/2 inhibitors for hemoglobinopathies

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL118917-01
Agency Tracking Number: R41HL118917
Amount: $367,972.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA12-089
Timeline
Solicitation Year: 2013
Award Year: 2013
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
SEAPORT CENTER 70 FARGO STREET
BOSTON, MA 02210-
United States
DUNS: 23556922
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MATTHEW JARPE
 (303) 398-1772
 mjarpe@acetylon.com
Business Contact
 ELAINE LARSEN
Phone: (617) 245-1313
Email: elarsen@acetylon.com
Research Institution
 BOSTON UNIVERSITY
 
BOSTON UNIVERSITY 881 COMMONWEALTH AVENUE
BOSTON, MA 02215-
United States

 () -
 Nonprofit College or University
Abstract

DESCRIPTION (provided by applicant): The long term goal of this project is a selective Histone Deacetylase 1 and 2 (HDAC1/2) inhibitor for the treatment of patients with the beta-hemoglobinopathies sickle cell anemia and beta- thalassemia. An estimated 400,000 children are born each year with one of these hemoglobin disorders. Few treatments exist to alleviate the symptoms of hemoglobinopathies and none are approved for children. Sickle cell anemia and beta-thalassemia remain an unmet medical need and a large public health burden. Reactivation of the expression of fetal hemoglobin can reverse many of the symptoms of beta hemoglobinopathies. Thus far treatments that induce expression of fetal hemoglobin also decrease or disrupt normal cell division and are associated with severe side effects. Recently the role of HDAC1 and 2 in the suppression of fetal hemoglobin expression was shown by genetic ablation of these genes. Compounds that are selective for HDAC1 and 2 versus other HDACs can induce the expression offetal globin in adult erythroid cells. We have generated a set of selective HDAC1/2 inhibitors with drug like properties. We plan to advance one of these compounds into pre-clinical development for beta hemoglobinopathies. We will test the activity of these compounds at inducing fetal globin gene expression in adult erythroid cells. We will also determine if this induction of fetal globin is accompanied by changes in erythroid cell division or differentiation. We will confirm that our compounds can inducefetal hemoglobin in cells from patients with beta-hemoglobinopathies. Finally, we will explore the mechanism of action of HDAC1/2 inhibition by examining changes in chromatin structure and function in the beta globin locus. The final product of this PhaseI project will be a selective HDAC1/2 inhibitor that can induce fetal hemoglobin in adult erythroid cells that will be advanced as a candidate for pre-clinical development. A Phase II project building off of this work would further advance the molecule through development toward filing of an IND for beta hemoglobinopathies. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: An estimated 400,000 children are born each year with one of these hemoglobin disorders. Few treatments exist to alleviate thesymptoms of hemoglobinopathies and none are approved for children. Sickle cell anemia and beta-thalassemia remain an unmet medical need and a large public health burden. This project aims to generate an inhibitor of histone deacetylase 1 and 2 as a new therapeutic for these hemoglobinopathies.

* Information listed above is at the time of submission. *

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