A targeted drug for the treatment of inflammation in cystic fibrosis lung disease

治疗囊性纤维化肺病炎症的靶向药物

• 批准号: 9136899
• 负责人: Charles Richard Esther
• 金额: $ 22.5万
• 依托单位: NANOMETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9136899
• 关键词: Affect; Affinity; American; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-inflammatory; Biochemical; Biological Sciences; Biotechnology; Clinic; Clinical; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Defect; Defense Mechanisms; Development; Dose; Drug Kinetics; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Feedback; Funding; Genes; Genetic; Goals; Hereditary Disease; Human; Individual; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Influentials; Knowledge; Lung diseases; Marketing; Metabolism; Methionine; Morbidity - disease rate; Mus; Oral; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Phosphorylases; Polyamine Synthesis Inhibition; Polyamines; Pre-Clinical Model; Property; Publishing; Pulmonary Cystic Fibrosis; Recycling; Regulator Genes; Reporting; Role; Sampling; Severities; Severity of illness; Small Business Innovation Research Grant; Specificity; Testing; Therapeutic; Toxic effect; Treatment outcome; United States National Institutes of Health; airway inflammation; analog; combinatorial; commercial application; cystic fibrosis patients; design; drug market; genome wide association study; global health; improved; inflammatory marker; inhibitor/antagonist; insight; metabolomics; mortality; mouse model; new therapeutic target; novel; novel strategies; public health relevance; research study; small molecule; success; targeted treatment; technological innovation

 DESCRIPTION (provided by applicant): Problem to be Solved: Cystic fibrosis (CF) is a global health issue that affects over 70,000 people worldwide, including ~30,000 Americans. Lung disease, is the primary cause of morbidity and mortality in CF patients, and is characterized by intense inflammatory responses in the airways. The Product and Long-Term Goal: Nanometics LLC (dba PHD Biosciences) (PHD) is developing a targeted small molecule enzyme inhibitor as a therapeutic for inflammation in CF lung disease. It is anticipated that this new approach will be useful to mitigate inflammation in the airways of patients. The Technological Innovation: The PHD approach is unique to all other CF therapeutics, utilizing a targeted enzyme inhibitor with high specificity and picomolar affinity to block recycling of an endogenous metabolite. Metabolite accumulation leads to robust and sustained anti-inflammatory activity. Phase I Hypotheses: This Phase I SBIR will demonstrate the feasibility of the PHD enzyme inhibitor as an oral therapeutic in Scnn1b-Tg mouse models of CF lung disease. The hypotheses tested during Phase I SBIR experiments will be: (1) a single oral dose will ameliorate inflammation for ≥ 24 h; and (2) once daily oral doses of the therapeutic are non-toxic and will promote a continued anti-inflammatory state. Specific Aims: Specific Aim #1. Demonstrate the Pharmacological and Concentration Dependent Effects of Oral Doses of MTDIA in the Scnn1b-Tg Mouse. Phase II: Phase II SBIR studies will further establish the mechanism of action and toxicity profile. Commercial Application: The PHD approach is a unique approach to anti-inflammatory therapy that will provide an extended benefit to patients as a single agent or part of a combinatorial approach. The current CF drug market is predicted to reach $3.9 billion by 2019.