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A novel therapeutic for the treatment of biofilms in periprosthetic joint infections

一种治疗假体周围关节感染生物膜的新型疗法

基本信息

批准号：
10760952
负责人：
Jessica Gilbertie
金额：
$ 30万
依托单位：
QENTOROS, LLC
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：
2023-09-07 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10760952
关键词：
Aftercare Amputation Animal Model Anti-Bacterial Agents Anti-Inflammatory Agents Antibiotics Autologous Bacteria Biological Blood Platelets Cartilage Chronic Clinical Trials Communities Complication Data Debridement Degenerative polyarthritis Development Donor Selection Ensure Equus caballus Extracellular Matrix Femur Goals Health Care Costs Human Human Activities Impairment Implant In Vitro Infection Inflammation Innate Immune Response Investigational New Drug Application Joints Literature Microbial Biofilms Modeling Morbidity - disease rate Musculoskeletal Names Operative Surgical Procedures Orthopedics Oryctolagus cuniculus Patients Periprosthetic joint infection Pharmaceutical Preparations Phase Plasma Population Procedures Property Refractory Replacement Arthroplasty Reporting Safety Staphylococcus aureus Staphylococcus aureus infection Stifle joint Synovial Fluid T-Lymphocyte Techniques Testing Therapeutic Tissues Treatment Failure Whole Blood Work aggressive therapy antimicrobial chronic infection clinical efficacy cost efficacy evaluation efficacy testing efficacy validation good laboratory practice healing immunogenicity implant material improved in vivo in vivo Model innovation joint infection manufacture mortality novel novel therapeutics porcine model pre-clinical preclinical study programs standard of care success

项目摘要

PROJECT SUMMARY Total joint arthroplasty (TJA) procedures are estimated to rise by over 300% by the year 2030. Periprosthetic joint infection (PJI) is the most significant complication following TJA with healthcare costs exceeding $1.6 billion annually. Treatment of PJI generally requires surgical intervention combined with a prolonged course of antibiotics costing $50,000 per patient. Despite this aggressive treatment, treatment is only successful in half of patients. The leading cause of treatment failure in PJI is the formation of protective bacterial biofilms or communities of bacteria encased within an extracellular matrix which are tolerant to commercially available antibiotics. We have discovered that platelet-rich plasma (PRP) displays both antibacterial and antibiofilm properties. Nevertheless, there is tremendous variability in the literature on the clinical efficacy of PRP. To overcome this variability, we have developed a PRP-derived biologic that is specifically formulated with high antimicrobial and anti-inflammatory activity with little to no lot-to-lot variability, termed BIO-PLY™. In an equine model of native joint infection, BIO-PLY™ not only decreased intraarticular bacterial load but also dampened inflammation and protected venerable cartilage from damage. In this proposal, we will capitalize on the equine model of native joint infection to manufacture a human equivalent and evaluate the safety and efficacy of human BIO-PLY™ using established in vitro and in vivo models of PJI. The goal of this proposal is to generate the key data necessary for a go/no-go decision to advance BIO-PLY™ toward a Phase II pre-clinical animal model and an Investigational New Drug (IND) application with the Federal Drug Administration.

项目概要预计到 2030 年，全关节置换术 (TJA) 手术将增加 300% 以上。关节感染 (PJI) 是 TJA 后最严重的并发症，医疗费用超过 16 亿美元每年。 PJI 的治疗通常需要手术干预并结合长期疗程每位患者的抗生素费用为 50,000 美元。尽管采取了这种积极的治疗，但治疗只有一半成功患者。 PJI 治疗失败的主要原因是保护性细菌生物膜的形成或包裹在细胞外基质内的细菌群落，能够耐受市售的细菌抗生素。我们发现富含血小板的血浆 (PRP) 具有抗菌和抗生物膜作用特性。然而，关于 PRP 临床疗效的文献存在巨大差异。到为了克服这种变异性，我们开发了一种 PRP 衍生的生物制剂，该生物制剂采用高浓度专门配制而成。抗菌和抗炎活性，批次间差异很小甚至没有，称为 BIO-PLY™。在马科动物中在天然关节感染模型中，BIO-PLY™ 不仅减少了关节内细菌负荷，而且还抑制了炎症并保护古老的软骨免受损伤。在这个提案中，我们将利用马天然关节感染模型，用于制造人类等效物并评估人类的安全性和有效性 BIO-PLY™ 使用已建立的 PJI 体外和体内模型。该提案的目标是生成密钥为将 BIO-PLY™ 推向 II 期临床前动物模型而做出通过/不通过决策所需的数据，以及向联邦药物管理局提交研究性新药 (IND) 申请。