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POP2 as a novel therapeutic in rheumatoid arthritis

POP2 作为类风湿关节炎的新型治疗方法

基本信息

批准号：
10524468
负责人：
JONATHAN A HARTON
金额：
$ 21.52万
依托单位：
ALBANY MEDICAL COLLEGE
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：
2022-09-23 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10524468
关键词：
Affect American Anti-Inflammatory Agents Antiinflammatory Effect Arthritis Atherosclerosis Autoimmune Diseases Autoimmunity Biochemical Biological Response Modifier Therapy Cartilage Cell Culture Techniques Cells Characteristics Chromosome 3 Chronic Clinical Code Collagen Arthritis Data Disease Dose Event Genes Gold Human Immunity Immunologics In Vitro Incidence Individual Infiltration Inflammasome Inflammation Inflammatory Inflammatory Response Inflammatory Response Pathway Interleukin-1 Interleukin-1 beta Interleukin-18 Interleukin-6 Investigation Joints Knowledge Laboratory Animals Longevity Measures Mediating Metabolic Diseases Modeling Molecular Mus NF-kappa B Non-Insulin-Dependent Diabetes Mellitus Outcome Pathology Pathway interactions Patients Peptides Pre-Clinical Model Primates Production Property Proteins Publishing Quality of life Recombinants Regimen Reporting Rheumatoid Arthritis Route Severities Signal Transduction Source Stimulus Synovial Membrane System TNF gene Tertiary Protein Structure Therapeutic Therapeutic Uses Transgenic Mice Treatment Protocols United States base bone erosion comorbidity cytokine experience improved in vivo inducible gene expression infection risk insight joint injury loss of function macrophage marenostrin mouse model novel novel therapeutic intervention novel therapeutics overexpression pre-clinical preclinical study stem targeted treatment transcription factor

项目摘要

Project Summary: Inflammation underlies the disabling manifestations and co-morbidities of rheumatoid arthritis (RA). Treatment regimens for RA patients aim to control inflammation and progressive joint damage mediated by inflammatory cytokines including TNFα, IL-1β, and IL-6. Recent studies demonstrate that humans possess four genes coding Pyrin-only proteins (POPs) that limit NF-B signaling and inflammasome activation pathways, events critical for elaboration of the cytokines mediating inflammation. TNF, IL-1β, and IL-6 are critically regulated by NF-B transcription factors. We have previously described the anti-inflammatory properties of POP2 in-vitro and in-vivo. Here we propose proof-of-concept studies to evaluate how POP2 and POP2-derived peptides impact experimentally induced RA when administered exogenously, using a murine preclinical model. POP2 peptide therapy represents a novel therapeutic approach to ameliorating excessive inflammation through dual inhibition of both NF-B signaling and inflammasome pathways. The immunological and molecular basis for our hypotheses stems from our published and preliminary data showing the naturally expressed, non-toxic POP2 peptide dampens cytokine production in inflammatory responses without compromising host immunity. Our studies will provide insight into how treatment regimens based on POP2 peptide therapy may be utilized or improved upon. In vitro characterization, dose-escalation studies and in-vivo assessment of disease parameters will inform approaches to develop POP2 peptides as a novel therapeutic.

项目总结: