Nonsurgical Exogenous Crosslink Therapy for Intervertebral Disc Disease

椎间盘疾病的非手术外源性交联疗法

基本信息

  • 批准号:
    7272176
  • 负责人:
  • 金额:
    $ 7.07万
  • 依托单位:
  • 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 2008-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Degenerative disc disease and associated spinal instability are the major cause of chronic low back pain in western civilization. Surgical options, including artificial discs, have been disappointing and only a very small percentage of back pain sufferers (~1 in 20) elect to have surgery. The specific aims of this program focus on the design of a nonsurgical tissue engineering solution that would become the first line of therapy for degenerative disc disease. Orthopeutics' key innovation is the use of nontoxic injectable agents that increase collagen crosslinking in the extracellular matrix of the disc annulus fibrosus, mimicking the body's own efforts to stabilize aged and mechanically unstable discs. Preliminary in vitro studies which form the basis of this Phase I proposal show a 2 to 3-fold improvement in durability, a 4-fold improvement in joint stability, and doubled nutritional supply/waste removal to center of the disc. In vivo proof of concept studies have demonstrated a mild treatment effect, with no significant histological changes in the annulus fibrosus. This Phase I study will characterize several candidate reagents with regard to crosslinking effect and diffusive transport using an ex vivo bovine/porcine disc model. Crosslinking effect will be assessed through mechanical testing, thermal analysis, and protease digestion. Diffusive transport will be assessed through time lapse visualization studies using dyes of representative molecular weights, as well as mapping of treated discs using thermal analysis. A Phase II study of the most promising formulation would focus on optimizing reagent activity, durability of effect, and safety; and developing a product suitable for human clinical trials. Back pain and disability associated with spinal degeneration and instability is one of the costliest and most prevalent health problems. Between 4.7 percent (medical records) and 9.4 percent (population surveys) of the US population seeks professional health care annually (1990) for low back pain, a prospective patient population in excess of 15 million/year. In the face of this great unmet clinical need, the development of regenerative medicine techniques to reverse the process of spinal disc degeneration has been recognized as an important research opportunity by NIAMS.
描述(由申请人提供):退行性椎间盘疾病和相关的脊柱不稳定是西方文明中慢性腰痛的主要原因。包括人工椎间盘在内的手术选择一直令人失望,只有极少数背痛患者(约二十分之一)选择接受手术。该计划的具体目标集中于设计一种非手术组织工程解决方案,该解决方案将成为退行性椎间盘疾病的一线治疗方法。骨科的关键创新是使用无毒的注射剂来增加纤维环细胞外基质中的胶原蛋白交联,模仿人体自身稳定老化和机械不稳定椎间盘的努力。构成这一第一阶段提案基础的初步体外研究表明,耐用性提高了 2 至 3 倍,关节稳定性提高了 4 倍,椎间盘中心的营养供应/废物清除增加了一倍。体内概念验证研究已证明其具有温和的治疗效果,纤维环没有明显的组织学变化。该第一阶段研究将使用离体牛/猪椎间盘模型来表征几种候选试剂的交联效应和扩散运输。将通过机械测试、热分析和蛋白酶消化来评估交联效果。将通过使用代表性分子量的染料的延时可视化研究以及使用热分析对处理过的圆盘进行绘图来评估扩散传输。对最有前途的配方进行的 II 期研究将侧重于优化试剂活性、效果的持久性和安全性;并开发适合人体临床试验的产品。 与脊柱退化和不稳定相关的背痛和残疾是最昂贵和最普遍的健康问题之一。每年(1990 年)美国有 4.7%(医疗记录)到 9.4%(人口调查)的人口因腰痛寻求专业医疗保健,预计患者人数每年超过 1500 万。面对这一巨大的未满足的临床需求,开发再生医学技术来逆转椎间盘退变过程已被NIAMS认为是一个重要的研究机会。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Thermal analysis reveals differential effects of various crosslinkers on bovine annulus fibrosis.
热分析揭示了各种交联剂对牛纤维环纤维化的不同影响。
Optimization of protein crosslinking formulations for the treatment of degenerative disc disease.
用于治疗退行性椎间盘疾病的蛋白质交联配方的优化。
  • DOI:
    10.1097/brs.0b013e3181cc3de9
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Slusarewicz,Paul;Zhu,Keng;Kirking,Bryan;Toungate,Justin;Hedman,Tom
  • 通讯作者:
    Hedman,Tom
Kinetic characterization and comparison of various protein crosslinking reagents for matrix modification.
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THOMAS P HEDMAN其他文献

THOMAS P HEDMAN的其他文献

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{{ truncateString('THOMAS P HEDMAN', 18)}}的其他基金

Crosslink augmentation to resist snoring and obstructive sleep apnea syndrome
交联增强可抵抗打鼾和阻塞性睡眠呼吸暂停综合症
  • 批准号:
    8452036
  • 财政年份:
    2013
  • 资助金额:
    $ 7.07万
  • 项目类别:
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
  • 批准号:
    7800652
  • 财政年份:
    2007
  • 资助金额:
    $ 7.07万
  • 项目类别:
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
  • 批准号:
    8018638
  • 财政年份:
    2007
  • 资助金额:
    $ 7.07万
  • 项目类别:
Modification of Intervertebral Disk Fatigue Resistance
椎间盘抗疲劳性的改进
  • 批准号:
    6403094
  • 财政年份:
    2001
  • 资助金额:
    $ 7.07万
  • 项目类别:

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