Investigating Disease Activity, Bone Damage and Interleukin-1 Genes in Adult SAPHO Syndrome and Chronic Nonbacterial Osteomyelitis

研究成人 SAPHO 综合征和慢性非细菌性骨髓炎的疾病活动、骨损伤和白细胞介素 1 基因

• 批准号: 10722534
• 负责人: Aleksander Lenert
• 金额: $ 16.74万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722534
• 关键词: Acne; Address; Adult; Agreement; Area; Binding; Bioinformatics; Childhood; Chronic; Clinic; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials; Code; Data; Development; Diagnosis; Disease; Early Diagnosis; Early Intervention; Effectiveness; Environment; Etiology; FDA approved; Future; Genes; Genetic; Genotype; Goals; Hyperostosis; IL1B gene; Image; Immunosuppression; Inflammation; Inflammatory; Infrastructure; Interleukin-1; Iowa; Joints; Knowledge; Large-Scale Sequencing; Lesion; Magnetic Resonance Imaging; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Multicenter Studies; Mutation; Observational Study; Osteitis; Osteomyelitis; Outcome; Pain; Pathogenicity; Pathway interactions; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Positioning Attribute; Predictive Value; Productivity; Prospective Studies; Psychometrics; RNA Splicing; Reference Standards; Reporting; Research; Research Design; Research Methodology; Research Personnel; Rheumatism; Risk; Risk Factors; Role; Science; Signaling Protein; Site; Specificity; Spinal Diseases; Statistical Data Interpretation; Sterility; Symptoms; Syndrome; Synovitis; Systemic Scleroderma; Techniques; Testing; Training; Translational Research; Universities; Variant; Visit; Work; autoinflammatory diseases; bone; career; career development; chronic pain; clinical phenotype; cohort; design; disability; disease phenotype; experience; follow-up; genetic variant; genome sequencing; imaging modality; improved; inhibitor; longitudinal course; modifiable risk; novel; novel marker; observational cohort study; patient oriented; prospective; recruit; skills; stem; targeted treatment; tool; treatment guidelines; treatment response; treatment strategy; variant detection; whole genome

Project Summary     SAPHO syndrome and chronic nonbacterial osteomyelitis (SAPHO-­CNO) is a painful and disabling  autoinflammatory disease primarily targeting bones and joints, with no FDA-­approved therapies. Severe sterile  inflammation of multiple bones (osteitis), driven by the interleukin-­1 (IL-­1) pathway, leads to irreversible bone  damage, chronic pain and disability in adult patients. Critical knowledge gaps remain about disease activity  assessments, risk factors for severe outcomes, and influence of variants in IL-­1 pathway genes on clinical  phenotypes in adults. This K23 proposal will propel our understanding of the longitudinal course of SAPHO-­ CNO in adults, garnering generalizable knowledge about this understudied and disabling autoinflammatory  disease. The proposed project will investigate clinician, patient and MRI-­assessed disease activity in a large  SAPHO-­CNO cohort (Aim 1), identify risk factors for bone damage in SAPHO-­CNO patients (Aim 2), and  discover IL-­1 signaling pathway gene variants and explore their correlation with clinical phenotypes in adults  with SAPHO-­CNO (Aim 3). The science resulting from this K23 award will lay the groundwork for a future R01  application. Dr. Aleksander Lenert is spearheading a unique prospective observational study in adult SAPHO-­ CNO (the SCS study) designed to address these knowledge gaps. His long-­term career goal is to develop into  an independent clinical investigator focused on patient-­oriented clinical and translational research in adults with  SAPHO-­CNO. Under direct mentorship from Dr. Polly Ferguson (world-­leading expert in CNO) and his  experienced mentoring team, Dr. Lenert will build on his foundational research skills to gain critical training and  hands-­on experience in agreement and psychometric analyses, latent trajectory modeling, genetic sequencing  analysis and interpretation, and prospective observational cohort study management. In addition to Dr.  Ferguson, his mentoring team includes Dr. Robyn T. Domsic (clinical investigator and observational cohort  study guru in systemic sclerosis), Dr. Daniel H. Solomon (leader in clinical science research in rheumatic  diseases), Dr. Mary Vaughan-­Sarrazin (experienced clinical outcomes researcher), and Dr. Jonathan Templin  (measurement science and applied psychometrics researcher). To further guide this scientific proposal,  develop focused training and aid his career development, Dr. Lenert has garnered the support of content area  experts in advanced imaging (Dr. T. Shawn Sato), and genetics and bioinformatics (Drs. Hatem El-­Shanti and  Benjamin Darbro). This proposal benefits from an exceptional scientific environment and established  infrastructure at the University of Iowa, including Dr. Polly Ferguson’s world-­renown center for the  management of patients with SAPHO-­CNO, and for clinical and translational research. Accomplishment of the  proposed Aims for this K23 award will directly benefit adults with SAPHO-­CNO, and lead to improved patient  outcomes. The K23 award will provide a framework for Dr. Lenert to acquire advanced methodologic research  skills and experiences necessary to become an independent clinical researcher in adult SAPHO-­CNO.

项目总结