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
基本信息
- 批准号:10722534
- 负责人:
- 金额:$ 16.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AcneAddressAdultAgreementAreaBindingBioinformaticsChildhoodChronicClinicClinicalClinical InvestigatorClinical ResearchClinical SciencesClinical TrialsCodeDataDevelopmentDiagnosisDiseaseEarly DiagnosisEarly InterventionEffectivenessEnvironmentEtiologyFDA approvedFutureGenesGeneticGenotypeGoalsHyperostosisIL1B geneImageImmunosuppressionInflammationInflammatoryInfrastructureInterleukin-1IowaJointsKnowledgeLarge-Scale SequencingLesionMagnetic Resonance ImagingMeasurementMeasuresMentored Patient-Oriented Research Career Development AwardMentorsMentorshipModelingMulticenter StudiesMutationObservational StudyOsteitisOsteomyelitisOutcomePainPathogenicityPathway interactionsPatient Outcomes AssessmentsPatient-Focused OutcomesPatientsPerformancePharmaceutical PreparationsPositioning AttributePredictive ValueProductivityProspective StudiesPsychometricsRNA SplicingReference StandardsReportingResearchResearch DesignResearch MethodologyResearch PersonnelRheumatismRiskRisk FactorsRoleScienceSignaling ProteinSiteSpecificitySpinal DiseasesStatistical Data InterpretationSterilitySymptomsSyndromeSynovitisSystemic SclerodermaTechniquesTestingTrainingTranslational ResearchUniversitiesVariantVisitWorkautoinflammatory diseasesbonecareercareer developmentchronic painclinical phenotypecohortdesigndisabilitydisease phenotypeexperiencefollow-upgenetic variantgenome sequencingimaging modalityimprovedinhibitorlongitudinal coursemodifiable risknovelnovel markerobservational cohort studypatient orientedprospectiverecruitskillsstemtargeted treatmenttooltreatment guidelinestreatment responsetreatment strategyvariant detectionwhole genome
项目摘要
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.
项目摘要
SAPHO 综合征和慢性非细菌性骨髓炎 (SAPHO-CNO) 是一种痛苦且致残的疾病
自身炎症性疾病主要针对骨骼和关节,尚无 FDA 批准的治疗方法。 严重无菌
由白细胞介素 1 (IL-1) 通路驱动的多处骨骼炎症(骨炎)会导致骨不可逆
成年患者的损伤、慢性疼痛和残疾。 关于疾病活动的关键知识差距仍然存在
评估、严重后果的风险因素以及 IL-1 通路基因变异对临床的影响
成人的表型。 这个 K23 提案将促进我们对 SAPHO 纵向路线的理解
CNO 在成人中,获得关于这一尚未充分研究的普遍知识并禁用自身炎症
疾病。 拟议的项目将调查临床医生、患者和 MRI 评估的大规模疾病活动
SAPHO-CNO 队列(目标 1),确定 SAPHO-CNO 患者骨损伤的风险因素(目标 2),以及
发现 IL-1 信号通路基因变异并探索它们与成人临床表型的相关性
与 SAPHO-CNO(目标 3)。 K23 奖项产生的科学成果将为未来的 R01 奠定基础
应用。 Aleksander Lenert 博士带头在成人 SAPHO 中开展一项独特的前瞻性观察研究 -
CNO(SCS 研究)旨在解决这些知识差距。 他的长期职业目标是发展成为
一位独立的临床研究者,专注于以患者为导向的成人临床和转化研究
SAPHO-CNO。 在 Polly Ferguson 博士(世界领先的 CNO 专家)和他的直接指导下
莱纳特博士拥有经验丰富的指导团队,他将在其基础研究技能的基础上获得关键培训和
协议和心理分析、潜在轨迹建模、基因测序方面的实践经验
分析和解释,以及前瞻性观察队列研究管理。 除了博士。
Ferguson 的指导团队包括 Robyn T. Domsic 博士(临床研究者和观察组)
系统性硬化症研究大师)Daniel H. Solomon 博士(风湿病临床科学研究的领导者)
疾病)、Mary Vaughan-Sarrazin 博士(经验丰富的临床结果研究员)和 Jonathan Templin 博士
(测量科学和应用心理测量学研究员)。 为了进一步指导这一科学提案,
莱纳特博士开展有针对性的培训并帮助他的职业发展,并获得了内容领域的支持
先进成像专家(T. Shawn Sato 博士)、遗传学和生物信息学专家(Hatem El-Shanti 博士和
本杰明·达布罗)。 该提案受益于特殊的科学环境并建立
爱荷华大学的基础设施,包括波莉·弗格森博士世界著名的中心
SAPHO-CNO 患者的管理以及临床和转化研究。 成就
K23 奖项的拟议目标将直接使 SAPHO-CNO 成人受益,并改善患者的病情
结果。 K23 奖将为 Lenert 博士提供一个获得先进方法研究的框架
成为成人 SAPHO-CNO 独立临床研究员所需的技能和经验。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Aleksander Lenert其他文献
Aleksander Lenert的其他文献
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