Commercialization of a Diagnostic test for amyotrophic lateral sclerosis (ALS)

描述(申请人提供)：肌萎缩侧索硬化症(ALS或Lou Gehrig病)是一种致命的神经退行性疾病，典型的寿命为确诊后3-5年。最初的症状可能类似于许多其他神经疾病，通常始于四肢无力、肌肉痉挛或言语或呼吸困难增加。目前还没有明确的ALS诊断测试，临床诊断通常 从症状出现起需要12个月的时间，并依赖于排除临床症状的其他潜在原因。更早的诊断将允许更快地开始使用新药治疗 正在开发的治疗方法，或者同样重要的是，提供了一种快速排除ALS作为症状原因的方法。铁马诊断公司的成立是为了最终完成ALS诊断和预后指标的开发，并在临床实验室改进修正案(CLIA)认证的实验室中将这些分析作为实验室开发测试(LDT)进行销售。我们已经发表了一系列同行评议的出版物，令人信服地证明在ALS患者的血液和脑脊液中可以检测到显著水平的pNfH和补体c3，并且我们的检测结果为ALS提供了诊断工具。我们提出了一系列任务，以在CLIA认证的实验室中优化和验证我们的分析，这是商业化之前的最后步骤。这是一个FastTrack应用程序，因为第三阶段之前的其余步骤都用高度可定义的通过/不通过门进行了很好的定义。在拟议工作的第一阶段，我们将最终确定和优化作为ALS诊断指标的检测，方法是测试样本中的指示蛋白，并将检测技术转换到一个新的平台上。第二阶段将在此基础上进行一项多中心前瞻性临床研究研究，并在CLIA认证的实验室中使用患者样本对分析进行鉴定，以确定ALS诊断的总体准确性。这项建议的目标是为这些生物标记物生成敏感和有效的LDT(实验室开发测试)，这些生物标记物在CLIA认证的实验室中用于临床诊断ALS。经过认证的LDT将作为一项服务向临床医生销售。

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a fatal neurodegenerative disease with a typical lifespan of 3 - 5 years after diagnosis. The initial symptoms can be similar to many other neurologic disorders and often begin with limb weakness, muscle fasciculations, or increasing difficulties in speech or breathing. No definitive diagnostic tests currently exist for ALS, and clinical diagnosis typically takes 12 months from symptom onset and relies on ruling out other potential causes of the clinical symptoms. Earlier diagnosis will permit more rapid initiation of treatment with newer drug therapies in development, or equally important provide a means to rapidly rule out ALS as a cause of the symptoms. Iron Horse Diagnostics, Inc. was created to finalize the development of diagnostic and prognostic indicators of ALS and market these assays as laboratory developed tests (LDTs) in a Clinical Laboratory Improvement Amendments (CLIA) certified lab. We have produced a series of peer-reviewed publications convincingly demonstrating that significant levels of pNfH and complement c3 can be detected in the blood and CSF of ALS patients, and that the levels detected by our assays provide diagnostic utility for ALS. We propose a series of tasks to optimize and validate our assays in a CLIA certified laboratory, the last remaining steps before commercialization. This is a FastTrack application because the remaining steps before Phase III are well defined with highly definable go/no-go gates. During Phase I of the proposed work, we will finalize and optimize assays as diagnostic indicators of ALS by testing samples for indicative proteins and translating the assay technology onto a new platform. Phase II will expand on this by conducting a multi-center prospective clinical research study and qualifying the assays using patient samples in a CLIA-certified lab to determine the overall accuracy of the ALS diagnostic. The goal of this proposal is to generate a sensitive and validated LDT (Lab Developed Test) for these biomarkers useful for clinically diagnosing ALS in a CLIA certified lab. A certified LDT will be marketed to clinicians as a service.