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in vivo Studies of Clinical Stage Globin Modulators

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2011 / STTR
Agency Tracking Number:
R41HL110727
Solicitation Year:
2011
Solicitation Topic Code:
NHLBI
Solicitation Number:
PA10-051
Small Business Information
PHOENICIA BIOSCIENCES, INC.
45 Beaver Rd WESTON, MA 02493-1017
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Woman-Owned: Yes
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2011
Title: in vivo Studies of Clinical Stage Globin Modulators
Agency: HHS
Contract: 1R41HL110727-01
Award Amount: $304,344.00
 

Abstract:

DESCRIPTION (provided by applicant): Inherited disorders which decrease production or alter structure of the 2-chain of hemoglobin A (2-thalassemias or sickle cell disease) are among the most common monogenic diseases in the world, afflicting millions worldwide, and are designated by WHO as a global health burden. Fetal hemoglobin (HbF: 12, 32) is another type of hemoglobin which is present in all humans, but is normally suppressed in infancy to levels below 2%. Decades of biochemical, clinical, and epidemiologic research have shown that any incremental increase in HbF reduces the severity of sickle cell disease, or reduces the life-threatening anemia of 2-thalassemia. Pharmacologic augmentation of fetal hemoglobin (3-globin chain) production, to replace thedefective or missing 2-globin chains, is established as a therapeutic modality. A small panel of therapeutic agents of different chemical classes can induce HbF experimentally, and a few have been tested clinically. Classes of agents shown to induce HbFin sickle cell disease and beta-thalassemia include: cytotoxic chemotherapeutic agents (such as hydroxyurea (HU), 5-azacytidine, and decitabine), short chain fatty acids (SCFAs) and derivatives (SCFADs), and some HDAC inhibitors. Some have shown proof-of-principle in reducing hospitalizations and transfusion dependency, but, except for HU, require parenteral administration or large doses, or are cytotoxic and mutagenic, and have not proven suitable for broad application. Further, any new chemical entities require costly toxicology and development costs for FDA approval. We recently developed and utilized a novel high-throughput screening program to interrogate a chemical library of drugs which are already FDA-approved for other conditions, and identified aselect panel of novel, and previously unrecognized potent HbF-inducing drugs some of which have benign safety profiles. The activity was validated in a secondary gene assays, erythroid cell culture, and in a pilot study in baboons. This proposal is to confirm and compare the efficacy of 3 candidate HbF-inducers in a nonhuman primate model which has been predictive of subsequent human responses for other drugs. This will allow selection of a therapeutic for rapid clinical application. Our Aims include: Aim I: To determine comparative in vivo activity of the candidate therapeutics in anemic nonhuman primates. Aim II: To prepare a medicinal formulation of the selected therapeutic PUBLIC HEALTH RELEVANCE: This proposal will evaluate three therapeutics fora new medical use in an animal model that simulates sickle cell disease and beta thalassemia, serious blood diseases worldwide. The therapeutics are already approved for other conditions. Upon completion of the proposed studies, the most potent agent canbe tested in the patient populations, and a new therapy can be rapidly applied to patient care.

Principal Investigator:

Susan P. Perrine
617-638-5639
sperrine@bu.edu

Business Contact:

Susan P. Perrine
617-750-5946
sperrine@bu.edu
Small Business Information at Submission:

PHOENICIA BIOSCIENCES, INC.
45 Beaver Rd WESTON, MA 02493-1017

EIN/Tax ID: 126064016
DUNS: N/A
Number of Employees: N/A
Woman-Owned: Yes
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER
UNIVERSITY OF OKLAHOMA
HEALTH SCIENCES CENTER 1000 Stanton L. Young Blvd, Rm 121
OKLAHOMA CITY, OK 73117-1213
Contact: