Problem to be Solved: Sickle cell disease (SCD) is a global health issue that affects approximately 100,00 Americans and over 13 million people worldwide. As a chronic and multifactorial disease, it is characterized by a persistent milieu of oxidative stress, inflammation, recurrent and painful episodes of sickle crisis, and chronic vasculopathy. The disease places significant financial stress on the United States Healthcare system, with annual costs exceeding $1.1 billion. Each year in the U.S., there are approximately 200,000 emergency room visits by patients seeking treatment for pain crisis and other disease related complications. There remains an unmet need for new interventions that ameliorate chronic vasculopathy and reduce the frequency and severity of pain crises. Product and Long-term Goal: PHD-14 is a small molecule with an excellent safety profile in humans and is being repurposed by Nanometics (d.b.a. PHD Biosciences [PHD]) as a chronic oral therapeutic to improve vascular flow, reduce the frequency of pain crises, and ameliorate organ damage in SCD patients. Technological Innovation: PHD-14 can act by several mechanisms to improve vascular flow and preliminary studies have demonstrated that a single intraperitoneal (i.p.) dose causes statistically significant improvements in the hemodynamic parameters of Berkeley (BERK) mice under ambient conditions and hypoxia / reoxygenation challenged NY1DD mice. Phase I Objectives: This Phase I SBIR project aims to demonstrate the feasibility of oral doses of PHD-14 as a safe and effective therapeutic in BERK. Phase II studies will be guided by feedback from a pre- investigational new drug meeting with the Food and Drug Administration. Commercial Opportunity: Treatment options for SCD are limited and there remains a significant need for new drugs to improve patient outcomes. As infant death rates decrease in developing countries, the target market is expected to rise dramatically over the next 20 years.
Project Terms: Adult; Advanced Glycosylation End Products; Affect; American; Applications Grants; Biological Sciences; Biotechnology; Blood Vessels; Businesses; Centers for Disease Control and Prevention (U.S.); Chemistry; Child; Chronic; Clinical; Clinical Research; commercial application; cost; Death Rate; design; Developing Countries; Development; Diabetes Mellitus; Diabetic Nephropathy; diabetic patient; Disease; Disease model; Dose; Emergency department visit; Ensure; Event; Feedback; Frequencies; global health; Glutamine; Goals; Healthcare Systems; healthy volunteer; Hematology; hemodynamics; Human; hydroxyurea; Hypoxia; improved; infant death; Inflammation; Intervention; intraperitoneal; Investigational Drugs; Knowledge; Lead; Letters; meetings; Microvascular Dysfunction; Modeling; Monitor; mouse model; Mus; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; novel therapeutics; Oral; Organ; Outcome; Oxidative Stress; Pain; Pain management; Parents; Pathogenicity; Pathology; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Phase; phase 2 study; Physicians; pre-clinical; Property; Pyridoxamine; Reactive Oxygen Species; Recurrence; Research Project Grants; Rodent Model; Safety; Scientist; Severities; Sickle Cell Anemia; sickling; Small Business Innovation Research Grant; Small Business Technology Transfer Research; small molecule; Stress; success; technological innovation; Testing; Therapeutic; Toxic effect; Treatment Efficacy; Treatment outcome; United States; United States Food and Drug Administration; United States National Institutes of Health; Vascular Diseases;
