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New Agents for the Treatment on Mycobacteria Avium Infections

治疗鸟分枝杆菌感染的新药

基本信息

批准号：
10597233
负责人：
Dennis L. Wright
金额：
$ 30万
依托单位：
QUERCUS MOLECULAR DESIGN, LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10597233
关键词：
ADME Study Accounting Airborne Particulate Matter Animals Antibiotics Antimycobacterial Agents Biological Availability Chimera organism Clarithromycin Climate Clinical Collection Development Dihydrofolate Reductase Dose Drug Targeting Drug resistance Environment Environmental Exposure Enzymes Equation Evaluation Folic Acid Folic Acid Antagonists Formulation Genus Mycobacterium Goals Grant Growth Hematology Human Immunocompromised Host In Vitro Incidence Individual Infection Infectious Skin Diseases Inhalation Knowledge Lead Libraries Life Lung Lung diseases Lung infections Lymphatic Modeling Multienzyme Complexes Mycobacterium Infections Mycobacterium avium Mycobacterium avium Complex Mycobacterium avium-intracellulare Infection Mycobacterium intracellulare New Agents Organism Permeability Pharmaceutical Preparations Phase Population Positioning Attribute Preparation Prevalence Program Development Protein Isoforms Resistance Resistance profile Respiratory Tract Infections Route Safety Small Business Technology Transfer Research Soil Source System Therapeutic Treatment Cost United States Water Work alternative treatment aqueous candidate selection clinically relevant combat comorbidity cost efficacy evaluation efficacy study healthcare community in vitro Model in vitro activity in vivo in vivo Model in vivo evaluation lead candidate liposomal formulation mycobacterial nanomolar non-tuberculosis mycobacteria nucleic acid biosynthesis opportunistic pathogen pathogen physical property preclinical evaluation product development public health relevance safety study standard of care therapeutic development trend

项目摘要

Abstract: Non-Tuberculosis Mycobacteria (NTM) are responsible for widespread, life threatening infections of the lungs, skin, lymphatic and hematological systems. The rapid, global spread of resistant organisms has significantly reduced the number of agents that can be used effectively to treat these infections. Of specific clinical relevance are the slow-growing Mycobacterium avium complex (MAC) comprised of M. avium, M. intracellulare and M. chimaera. MACs are widely distributed throughout the environment, often found in soil, water and airborne particulates. Mycobacterial infections are a growing cause of concern in immunocompromised individuals with underlying comorbidities and represent a significant threat as opportunistic pathogens. Over the past three decades, the incidence of infections caused by MAC NTMs have increased more than 30-fold. Change in the world climate is allowing these once-unknown environmental mycobacteria to flourish and establish themselves as an increasingly common source of deadly infections, accounting for approximately 40% of the pulmonary infections (NTM lung disease) found in immunocompromised patients. Currently in the United States, the prevalence of MAC NTM infections is approximately 50 per 100,000 population, equating to more than 200,000 new cases annually. It is estimated that this number will grow at a rate of +8% per year. The costs associated with treatment of NTM-related infections exceeded $800M in 2018. MAC NTM-LD represents an unmet clinical need as there are few safe and effective drugs available to combat the infections they cause. Furthermore, because standard antibiotics have so much environmental exposure, many MAC isolates are natively drug resistant. QMD is focused on the development of an inhaled therapeutic that inhibits the essential NTM enzyme dihydrofolate reductase (DHFR), which is involved in the biosynthesis of the nucleic acid building blocks that are a key player in the folate cycle and a validated antibiotic drug target.

摘要：非结核分枝杆菌（NTM）是造成广泛的、危及生命的感染的原因