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HLS Cyclic CAR peptide a targeted therapy for pulmonary hypertension

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R42HL132742-01A1
Agency Tracking Number: R42HL132742
Amount: $302,402.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-08-15
Award End Date (Contract End Date): 2018-08-31
Small Business Information
4819 EMPEROR BLVD STE 400, Durham, NC, 27703-5420
DUNS: 112025965
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 PAUL YU
 (857) 307-0395
 pbyu@partners.org
Business Contact
 DAVID MANN
Phone: (919) 313-4826
Email: dmann@vascularbiosciences.com
Research Institution
 BRIGHAM AND WOMEN'S HOSPITAL
 75 FRANCIS STREET
BOSTON, MA, 02115-6110
 Domestic nonprofit research organization
Abstract
PUBLIC ABSTRACT This project in response to announcement HLS describes a development program for CARSKNKDC CAR a synthetic cyclic peptide that selectively targets diseased pulmonary vascular endothelium and enhances the therapeutic effect of vasodilator therapies for the treatment of pulmonary hypertension PH PH is a disorder of elevated pulmonary vascular resistance characterized by progressive thickening and obliteration of resistance determining vessels of the pulmonary circulation Despite current therapies survival following the diagnosis of PH remains slightly better than at years with mortality a result of disease progression and right heart failure Vasodilator therapies acting upon endothelin prostacyclin and nitric oxide pathways modestly improve functional status but are limited by systemic side effects toxicity and tachyphylaxis No current therapy selectively targets the diseased pulmonary circulation CAR whose peptide sequence has high sequence homology to protein heparin binding domains was identified by a phage screen for its enhanced binding to the vasculature of soft tissue wounds We have demonstrated that CAR accumulates in the endothelium and adventitia of pulmonary vessels in animals with PH but not systemic vessels and not the pulmonary vessels of normal animals When given with systemic vasodilator therapies CAR potentiates selective vasodilatation of the pulmonary vascular bed without increasing systemic vasodilation CAR peptide appears to enhance the delivery of drugs to diseased vessels by a co administration effect without requiring conjugation to drugs By virtue of its selective homing for damaged endothelium we propose that chronic administration CAR will synergize with prostacyclin and PDE inhibitor therapies with greater impact on pulmonary vascular remodeling We have devised a strategy that will optimize the dosing formulation and delivery pharmacokinetics and pharmacodynamics of this agent as an adjuvant therapy in combination with FDA approved vasodilator therapies for PH This potentially groundbreaking approach would constitute the first example of a targeted therapy specifically designed to address pulmonary vascular disease and could address limitations of current PH therapy Project Narrative Pulmonary hypertension describes a diverse set of diseases characterized by elevated pressures and progressive obstruction of the lung vessels with a survival of approximately years following diagnosis despite current treatments Current therapies are vasodilators that are not specific for lung vessels and are limited in their use by their tendency to lower pressure in all blood vessels and cause side effects or toxicity in other organs The current proposal examines a new type of drug molecule which targets only diseased lung blood vessels and which may improve the efficacy and reduce side effects of current treatments by concentrating their effects in diseased lung vessels

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

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