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Engineered Biotherapeutic Agent for Treatment of Post-Traumatic Osteoarthritis

用于治疗创伤后骨关节炎的工程生物治疗剂

基本信息

批准号：
10821518
负责人：
Jui Shivaji Chaugule
金额：
$ 13.73万
依托单位：
PROVIZIGEN 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：
2023-09-25 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10821518
关键词：
Acceleration Acute Address Adverse effects Adverse event Affect American Animal Model Animals Anterior Cruciate Ligament Anti-Inflammatory Agents Arthralgia Arthritis Behavior Biocompatible Materials Biodistribution Biological Products Biological Response Modifier Therapy Carrier Proteins Cartilage Cartilage Diseases Circular Dichroism Degenerative Disorder Degenerative polyarthritis Development Disease Progression Dose Engineering Exhibits Gait Gel Goals Growth Factor Hydrogels Hydrogen In Situ Inflammatory Injectable Injury Intra-Articular Injections Investigation Joint Instability Joints Life Expectancy Marketing Mechanics Micelles Modeling Molecular Structure Operative Surgical Procedures Oryctolagus cuniculus Outcome Pain Patients Pharmaceutical Preparations Phase Physicians Physiological Preparation Prevention Preventive care Preventive treatment Property Protein Engineering Proteins Public Health Rattus Reconstructive Surgical Procedures Replacement Arthroplasty Reproducibility Rheology Saline Scanning Electron Microscopy Second Look Surgery Small Business Technology Transfer Research Structure System TNF gene Temperature Therapeutic Therapeutic Effect Time Toxic effect Toxicology Trauma Traumatic Arthropathy Traumatic injury Treatment Cost Weight anterior cruciate ligament rupture arthropathies articular cartilage biopharmaceutical industry cartilage degradation cartilage repair chondroprotection commercial application cytokine density disability experience experimental group first-in-human good laboratory practice human disease joint inflammation joint injury light scattering minimally invasive novel point of care point of injury pre-clinical preclinical study preservation prevent product development viscoelasticity

项目摘要

PROJECT SUMMARY/ABSTRACT Post-traumatic osteoarthritis (PTOA) is a degenerative disease of cartilage brought on by traumatic injury to the articular joints. Acute joint injury is followed by severe joint pain and inflammation. This results in much more rapid degeneration of cartilage than in other forms of osteoarthritis, due to the joint instability caused by trauma as well as the increase in proinflammatory cytokines that accelerate degeneration. PTOA affects 5.6 million Americans, with an estimated $11.79 billion associated with direct treatment costs for its treatment. There are no approved treatments that stop or alter the progression of the disease, and complete degeneration of the articular cartilage can necessitate joint replacement surgery. This may require surgical revision in approximately 10 years, a particularly undesirable outcome in younger patients with longer life expectancies. ProViZiGen has developed a novel protein-engineered injectable therapeutic hydrogel system, HydroGEN that forms a gel when injected into the joint space and provides sustained delivery of an anti-inflammatory and chondroprotective therapeutic molecule. Our recent preclinical investigation in a rabbit anterior cruciate ligament (ACL) transection model has shown that immediate delivery of HydroGEN significantly prevents the development of PTOA after joint injury and delivery 8 weeks after the point of injury has therapeutic effects promoting endogenous cartilage repair. In this Phase I STTR, we aim to determine stability and lack of toxicity of HydroGEN to establish functional gelation and establish safe dosing. In Aim I, we will determine the stability and mechanics of HydroGEN by assessing the protein’s microstructure and macrostructure, as well as its rheologic properties as a function of temperature and time to determine its functionality as an in situ gelling injectable therapeutic. In Aim II, we will establish the lack of toxicity and selective biodistribution of HydroGEN in a rat model of intraarticular injection. Successful completion of these aims will prepare ProViZiGen for filing a BLA with the FDA, with large animal PTOA model investigation (Phase II) leading to first in human trials.

项目总结/文摘