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Injectable collagen crosslink augmentation for degenerative disc disease

可注射胶原交联增强治疗退行性椎间盘疾病

基本信息

批准号：
8018638
负责人：
THOMAS P HEDMAN
金额：
$ 35.94万
依托单位：
ORTHOPEUTICS, LP
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8018638
关键词：
Acute Address Age Animal Model Animals Back Pain Biological Assay Blood Chemical Analysis Buffers Cattle Chemicals Clinical Clinical Trials Collagen Cross-Linking Reagents Crosslinker Data Digestion Disease Drug Formulations Effectiveness Extracellular Matrix Fatigue Fibrosis Funding Future Goals Health High Pressure Liquid Chromatography Human In Vitro Injectable Injection of therapeutic agent Intervertebral disc structure Investigation Joints Kinetics Life Low Back Pain Mechanics Modeling Modification Neurologic Nutritional Operative Surgical Procedures Penetration Peptide Hydrolases Pharmaceutical Preparations Phase Physical therapy Play Preparation Prevalence Rattus Reaction Reagent Resistance Role Small Business Innovation Research Grant Societies Solutions Spinal Structure Subcutaneous Injections Subgroup Testing Tissues Variant aged base biomaterial compatibility clinical care conditioning cost cost effective crosslink design disability effective therapy efficacy testing improved in vitro Assay in vivo intervertebral disk degeneration man neurotoxicity novel pandemic disease patient population peer prevent programs public health relevance reaction rate response success surfactant treatment effect

项目摘要

DESCRIPTION (provided by applicant): With regard to prevalence and cost to society, low-back pain has few peers. With a patient population in excess of 15 million/year, the societal cost is estimated to be in the realm of $100 billion/year. Current treatment options for this disease have shown limited success, including physical therapy, medication and surgery. This proposal involves a novel, nonsurgical and cost-effective, tissue revitalization approach which shows promise for treatment of mechanically and nutritionally challenged tissues like the spinal disc. Previous in vitro and in vivo studies have demonstrated the efficacy of Injectable collagen crosslink augmentation in stabilizing spinal joints, decreasing disc bulge under load, increasing the strength, tear resistance, and durability of the tissue, while also improving nutritional flow to these largely avascular tissues. Phase I testing was successful in characterizing the crosslinking effects of seven candidate agents in disc annulus fibrosis (AF) tissue using mechanical, thermal and protease digestion assays. At least one preferred agent was identified, and concentration, pH, conditioning, and buffering were optimized to maximize the efficiency of crosslinking and mechanical effect. Recently, in vitro assays have been undertaken to determine agent and buffer biocompatibility. The proposed Phase II testing will provide data necessary for regulatory filings and first-in-man clinical trials. Reagent delivery, penetration, reaction kinetics, permanency (effect duration), and storage requirements (shelf life) will be thoroughly investigated. Acute, functional biocompatibility and neurotoxicity studies will be conducted to quantify expected and worst-case treatment effects in an animal model. Further characterization of crosslinking effects will be determined using different subgroups of human AF tissues (variations in age, composition, degeneration). By bringing this path-breaking treatment to the doorstep of clinical trials, SBIR funding will play a vital role in enabling progress towards the ultimate goal of providing a novel, cost-effective treatment in the struggle against low back pain and disability. PUBLIC HEALTH RELEVANCE: Back pain and disability associated with spinal degeneration and instability remains among the most costly and prevalent health problems in the US today. With a patient population in excess of 15 million/year, the societal cost is estimated to be in the realm of $100 billion/year. Due to the limited success of current treatment options, it is reasonable to expect that an effective nonsurgical solution could revolutionize clinical care for this pandemic.

描述（由申请人提供）：就流行率和社会成本而言，腰痛是罕见的。由于每年患者人数超过 1500 万，社会成本估计达到每年 1000 亿美元。目前针对这种疾病的治疗方案，包括物理治疗、药物治疗和手术，效果有限。该提案涉及一种新颖的、非手术且具有成本效益的组织再生方法，该方法有望治疗椎间盘等机械和营养困难的组织。先前的体外和体内研究已经证明了可注射胶原交联增强剂在稳定脊柱关节、减少负载下椎间盘突出、增加组织的强度、抗撕裂性和耐久性方面的功效，同时还改善了这些基本上无血管组织的营养流动。第一阶段测试成功地利用机械、热和蛋白酶消化测定法表征了七种候选药物在椎间盘纤维化 (AF) 组织中的交联效应。确定了至少一种优选试剂，并优化了浓度、pH、调节和缓冲，以最大限度地提高交联效率和机械效应。最近，已经进行了体外测定以确定试剂和缓冲液的生物相容性。拟议的二期测试将为监管备案和首次人体临床试验提供必要的数据。将彻底研究试剂输送、渗透、反应动力学、持久性（作用持续时间）和储存要求（保质期）。将进行急性、功能性生物相容性和神经毒性研究，以量化动物模型中的预期和最坏情况治疗效果。交联效应的进一步表征将使用人类 AF 组织的不同亚组（年龄、成分、退化的变化）来确定。通过将这种开创性的治疗方法引入临床试验，SBIR 资金将在实现最终目标方面发挥至关重要的作用，即提供一种新颖的、具有成本效益的治疗方法来对抗腰痛和残疾。公共卫生相关性：与脊柱退化和不稳定相关的背痛和残疾仍然是当今美国最昂贵和最普遍的健康问题之一。由于每年患者人数超过 1500 万，社会成本估计达到每年 1000 亿美元。由于当前治疗方案的成功有限，有理由预期有效的非手术解决方案可能会彻底改变这一流行病的临床护理。