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A PDGFR inhibitor for the treatment of pulmonary arterial hypertension

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
96329
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
HL102946
Solicitation Year:
N/A
Solicitation Topic Code:
NHLBI
Solicitation Number:
N/A
Small Business Information
PULMOKINE, INC.
PULMOKINE, INC. 68 QUEEN ANNE DR SLINGERLANDS, NY 12159-9385
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: A PDGFR inhibitor for the treatment of pulmonary arterial hypertension
Agency: HHS
Contract: 1R43HL102946-01
Award Amount: $351,008.00
 

Abstract:

DESCRIPTION (provided by applicant): Pulmonary arterial hypertension (PAH) is a devastating disease associated with high morbidity and mortality. The purpose of this proposal is to develop a novel highly selective platelet derived growth factor receptor (P DGFR) inhibitor for PAH that will be delivered by inhalation. Signaling through the PDGFR leads to smooth muscle cell proliferation which contributes to the development of PAH. The PDGFR inhibitor imatinib has shown efficacy in treating PAH in some patient s. However, there are some concerns about off-target effects of imatinib because it also inhibits another kinase called Abl. The PDGFR inhibitors to be developed in this proposal are more selective than imatinib and do not inhibit Abl. This proposal will d evelop these novel inhibitors for direct pulmonary delivery. Because PAH involves the pulmonary arteriolar bed, direct delivery of the drug by inhalation will improve the therapeutic window: i.e., increase efficacy, and decrease systemic side effects. The approach will consist of the following steps: 1) Formulate the drug candidates for aerosolization and determine the respiratory deposition pattern of inhaled aerosol with SPECT gamma scintigraphy and three dimensional computed tomography. 2) Determine the inhaled and deposited mass of the drug candidates and pharmacokinetic distribution of the drug candidates. 3) Determine the efficacy and therapeutic window of lead drug candidates in a model of PAH. The effect of the drug candidates on pulmonary hypertensi on will be measured by continuous telemetry monitoring of pulmonary artery pressure. The effect of study drug on right ventricular function will be evaluated with echocardiography, and a new admittance technology to generate pressure-volume loops. Histolog y will be performed to evaluate the effect of the study drugs on the pulmonary pathology associated with PAH. The results of this project will lead to formulation of one of the lead candidates for use in humans and IND enabling studies. This new treatment could reduce the morbidity and mortality of PAH and thereby benefit patients and society. PUBLIC HEALTH RELEVANCE: Pulmonary arterial hypertension is a devastating disease with a high morbidity and mortality. This project is relevant to public heal th because it will ultimately lead to a new treatment for pulmonary arterial hypertension.

Principal Investigator:

Lawrence S. Zisman
5183318078
LZISMAN@MYOMATRIX.COM

Business Contact:

Lawrence M. Xisman
Small Business Information at Submission:

PULMOKINE, INC.
PULMOKINE, INC. 68 QUEEN ANNE DR SLINGERLANDS, NY 12159

EIN/Tax ID: 126141519
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No