Diagnostic Biomarkers for Radicular Pain

根性疼痛的诊断生物标志物

• 批准号: 7804457
• 负责人: Gaetano John Scuderi
• 金额: $ 19.23万
• 依托单位: CYTONICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804457
• 关键词: Absenteeism at work; Accounting; Address; Adrenal Cortex Hormones; American; Antibodies; Back; Back Pain; Biochemical; Biological Assay; Biological Markers; Biotechnology; Body part; Caring; Cauda Equina; Clinic; Clinical; Clinical Research; Degenerative Disorder; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Economic Burden; Enzyme-Linked Immunosorbent Assay; Esthesia; Etiology; Expenditure; Funding; Health Care Visit; Hospitalization; Inflammation Mediators; Inflammatory; Injection of therapeutic agent; Intervention; Intervertebral disc structure; Leg; Low Back Pain; Marketing; Mass Spectrum Analysis; Measures; Medical; Methods; Muscle strain; Musculoskeletal; Nerve; Neurologic; Occupations; Operative Surgical Procedures; Orthopedics; Pain; Pathogenesis; Pathology; Pathway interactions; Patients; Phase; Phase II Clinical Trials; Physicians; Plant Roots; Process; Proteins; Proteomics; Protocols documentation; Provider; Radiculopathy; Reagent; Reference Standards; Reproducibility; Resistance; Resolution; Rest; Sampling; Signal Transduction; Site; Small Business Innovation Research Grant; Source; Specific qualifier value; Spinal; Spinal Stenosis; Steroids; Structure; Surgical Decompression; Syndrome; Technology; Testing; Time; Vertebral column; Work; base; clinical care; disability; effective therapy; falls; innovation; intervertebral disk degeneration; irritation; medical attention; novel; novel diagnostics; product development; prospective; protein complex; prototype; public health relevance; research study; sample collection; treatment strategy; validation studies

DESCRIPTION (provided by applicant): Spinal related complaints are the most common reason for physician visits and healthcare expenditures. Conditions related to back pain account for more hospitalizations than any other musculoskeletal condition and the back is the body part most often involved in work-related disabilities. The spine market is the fastest growing market in orthopedics, creating a unique opportunity to commercialize innovative diagnostic and treatment technologies that are tailored towards specific clinical challenges. One of the greatest challenges for physicians is reaching an accurate diagnosis when faced with certain orthopedic problems. Spinal related sciatic pain can have multiple etiologies, creating diagnostic challenges. Various technologies exist to assist physicians to accurately diagnose these patients, but many are expensive, time consuming and require multiple trips to care providers. A rapid, less costly and accurate diagnosis would greatly benefit the patient. Cytonics Corporation is a privately held biotechnology company that has discovered a novel protein biomarker that not only identifies the source of radicular pain but also specifies an effective treatment course. Objectives during this SBIR Phase I funding period are to further characterize and validate a novel diagnostic biomarker for back pain syndromes that cause radiculopathy. Two Specific Aims are proposed to accomplish these objectives. The first Aim further characterizes a novel protein complex identified by Cytonics as a biomarker of pain caused by low back pain (LBP) syndromes. A standardized antibody based assay will be developed that specifically recognizes this new protein complex biomarker. The second Aim performs a prospective clinical research study to validate the diagnostic assay. Efficient and specific diagnostic tests for neurological root irritation caused by LBP syndromes that also indicate effective treatment strategies will fill an unmet medical need and establish Cytonics as a leader within a large and expanding marketplace. In addition, Cytonics will obtain invaluable information on disease pathogenesis and biochemical targets for the expeditious development of a next generation diagnostic assay and pharmacotherapeutic(s). PUBLIC HEALTH RELEVANCE: Low back pain (LBP) syndromes are one of the most common forms of pain and causes of disability. Americans spend at least $90 billion each year on low back pain, the most common cause of job-related disability and a leading contributor to missed work with an estimated economic burden in the US in hundreds of billions per year. There are many causes of back pain, and proper determination of the source of pain helps guide treatment strategies. Common causes of back pain include disc herniation, spinal stenosis, back muscle strain, and disc degeneration. Pathology of one or more lumbar intervertebral discs is thought to result in severe pain and abnormal sensations radiating from the nerve root down the leg (radiculopathy). Current methods to diagnose radiculopathy and determine proper treatment strategies (steroid injections, surgery, or rest and hope for pain resolution) are inadequate and therefore a very large market and unmet medical need exists. The overall objectives of this clinical proteomics study are to characterize and validate a novel protein complex as a biomarker for radicular pain that also identify patients that will respond to epidural steroid treatment. The objectives of Cytonics Corporation during this SBIR Phase I funding period is to address the following specific aims related to the diagnosis and treatment of LBP syndromes that cause neurological irritation: Aim 1: Further characterize our recently-identified biomarker protein complex and standardize the Cytonics diagnostic assay prototype for neurological root irritation caused by LBP syndromes. A) Additional mass spectrometry and antibody-based approaches will be used to further characterize the novel biomarker protein complex identified in our new preliminary studies. B) Reproducibility, sensitivity and accuracy are essential for robust biomarker detection. Thus, antibody reagents and assay reference standards must be tested to generate the best protocols to maximize diagnostic signal reproducibility and accuracy. These protocols and reagents will be used in all subsequent product development steps and for sample collection kits to be marketed to clinics. Aim 2: Perform a prospective clinical validation study for the Cytonics diagnostic assay. A) Collect patient samples in a multi-center clinical research study. B) Measure levels of the novel protein complex by ELISA generated in Aim 1. Completion of the proposed Specific Aims will enable Cytonics Corporation to create novel and proprietary diagnostic tests that can be rapidly brought to market during a subsequent SBIR Phase II protocol. Efficient and specific diagnostic tests for neurological root irritation caused by LBP syndromes that also indicate effective treatment strategies will fill an unmet medical need and establish Cytonics as a leader within a large and expanding marketplace. In addition, Cytonics will obtain invaluable information on disease pathogenesis and biochemical targets for the expeditious development of a next generation diagnostic assay and pharmacotherapeutic(s).

描述（由申请人提供）：脊柱相关投诉是医生就诊和医疗保健支出的最常见原因。与背痛相关的疾病比任何其他肌肉骨骼疾病都要多，背部是最常涉及与工作有关的残疾的身体部位。脊柱市场是骨科领域增长最快的市场，为针对特定临床挑战定制的创新诊断和治疗技术的商业化创造了独特的机会。医生面临的最大挑战之一是在面临某些骨科问题时做出准确的诊断。脊柱相关坐骨神经痛可能有多种病因，造成诊断挑战。有各种技术可以帮助医生准确诊断这些患者，但许多技术都很昂贵，耗时，并且需要多次前往护理提供者。快速、低成本和准确的诊断将使患者受益匪浅。Cytonics公司是一家私营生物技术公司，发现了一种新的蛋白质生物标志物，不仅可以识别神经根疼痛的来源，还可以指定有效的治疗过程。SBIR第一阶段资助期间的目标是进一步表征和验证导致神经根病的背痛综合征的新型诊断生物标志物。为实现这些目标，提出了两个具体目标。第一个目标进一步表征了一种由Cytonics鉴定的新型蛋白质复合物，作为腰痛（LBP）综合征引起的疼痛的生物标志物。将开发一种标准化的基于抗体的测定法，其特异性地识别这种新的蛋白质复合物生物标志物。第二个目的是进行前瞻性临床研究，以验证诊断测定。针对LBP综合征引起的神经根刺激的高效和特异性诊断测试也表明有效的治疗策略将填补未满足的医疗需求，并将Cytonics确立为大型和不断扩大的市场中的领导者。此外，Cytonics将获得有关疾病发病机制和生化靶点的宝贵信息，以快速开发下一代诊断检测和药物。 公共卫生相关性：腰痛（LBP）综合征是最常见的疼痛形式和残疾原因之一。美国人每年至少花费900亿美元用于腰痛，这是与工作有关的残疾的最常见原因，也是导致美国每年数千亿美元经济负担的主要原因。背痛的原因有很多，正确确定疼痛的来源有助于指导治疗策略。背痛的常见原因包括椎间盘突出、椎管狭窄、背部肌肉拉伤和椎间盘退变。一个或多个腰椎间盘的病理被认为会导致剧烈疼痛和从神经根向下辐射到腿部的异常感觉（神经根病）。目前诊断神经根病和确定适当治疗策略（类固醇注射、手术或休息并希望疼痛消退）的方法是不够的，因此存在非常大的市场和未满足的医疗需求。这项临床蛋白质组学研究的总体目标是表征和验证一种新型蛋白质复合物作为神经根性疼痛的生物标志物，该生物标志物还可识别对硬膜外类固醇治疗有反应的患者。在SBIR第一阶段资助期间，Cytonics公司的目标是解决以下与导致神经刺激的LBP综合征的诊断和治疗相关的具体目标：目标1：进一步表征我们最近发现的生物标志物蛋白复合物，并标准化Cytonics诊断分析原型，用于LBP综合征引起的神经根刺激。A）额外的质谱和基于抗体的方法将用于进一步表征在我们新的初步研究中鉴定的新型生物标志物蛋白质复合物。B）再现性、灵敏度和准确度对于稳健的生物标志物检测是必不可少的。因此，必须测试抗体试剂和测定参比标准品，以生成最佳方案，从而最大限度地提高诊断信号的再现性和准确性。这些方案和试剂将用于所有后续产品开发步骤以及向诊所销售的样本采集试剂盒。目的2：对Cytonics诊断测定进行前瞻性临床验证研究。A）在多中心临床研究中收集患者样本。B）通过ELISA测量目标1中产生的新蛋白质复合物的水平。完成拟议的特定目标将使Cytonics Corporation能够创建新的专有诊断测试，这些测试可以在随后的SBIR第二阶段协议中迅速推向市场。针对LBP综合征引起的神经根刺激的高效和特异性诊断测试也表明有效的治疗策略将填补未满足的医疗需求，并将Cytonics确立为大型和不断扩大的市场中的领导者。此外，Cytonics将获得有关疾病发病机制和生化靶点的宝贵信息，以快速开发下一代诊断检测和药物。