Initial results indicate that sodium nitrite can be used as a potential cost-effective platform therapy for a wide variety of disease indications characterized broadly by constricted blood flow or hypoxia.

Pulmonary Hypertension (PH) occurs as a primary or idiopathic disease as well as secondary to a number of pulmonary and systemic diseases, such as neonatal PH and sickle cell disease. There is no cure for pulmonary hypertension, a nitric-oxide deficient state characterized by pulmonary vasoconstriction and systemic hypoxemia and therapies vary in efficacy and cost. Recent studies by NIH researchers and their collaborators provided evidence that the blood anion nitrite contributes to hypoxic vasodilation through a heme-based, nitric oxide (NO)-generating reaction with deoxyhemoglobin and potentially other heme proteins [Nature Medicine 2003 9: 1498-1505]. These initial results indicate that sodium nitrite can be used as a potential cost-effective platform therapy for a wide variety of disease indications characterized broadly by constricted blood flow or hypoxia. These results have been further corroborated by more recent work in the neonatal lamb model for PH. Inhaled sodium nitrite delivered by aerosol to newborn lambs with hypoxic pulmonary hypertension elicited a rapid and sustained reduction (65%) in hypoxia-induced pulmonary hypertension. Pulmonary vasodilation elicited by aerosolized nitrite was deoxyhemoglobin- and pH-dependent and was associated with increased blood levels of iron-nitrosyl-hemoglobin. Notably, short term delivery of nitrite dissolved in saline through nebulization produced selective, sustained pulmonary vasodilation with no clinically significant increase in blood methemoglobin levels. [Nature Medicine 2004 10: 1122- 1127]. This new, simple and cost-effective potential therapy for neonatal PH is available for licensing. Also available for licensing are claims directed to nitrite salt formulations associated with elevated blood pressure, decreased blood flow or hemolytic disease (HHS Ref. No. E- 254-2003/2) as well as for the treatment of specific conditions including hepatic, cardiac or brain ischemia-reperfusion injury and other cardiovascular conditions [J. Clin. Invest. (2005) 115:1232-1240; JAMA (2005) 293: 1477-1484] (HHS Ref. No. E-254-2003/3).

PCT Applications filed 09 Jul 2004 (priority date 9 July 2003): PCT/US04/21985, International Publication No. WO 2005/007173, Publication Date 27 January 2005 [HHS Reference No. E-254-2003/2-PCT-01] and PCT/US04/22232, International Publication No. WO 2005/004884, Publication Date 20 January 2005 [HHS E-254- 2003/3-PCT-01] Inventors: M. Gladwin (CC), R. Cannon (NHLBI), A. Schechter (NIDDK), C. Hunter (CC), R. Pluta (NINDS), E. Oldfield (NINDS), et al.

Licensees sought. This technology is available for non- exclusive and exclusive licensing. Collaborative Research Opportunity: The National Heart, Lung, and Blood Institute, Vascular Medicine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a treatment of pulmonary hypertension (PH) using nitrite therapy. Please contact Dr. Mark Gladwin by phone at 301-435-2310 or by email at mgladwin@nih.gov for more information.