Multi-path DCS as a novel non-invasive treatment for amyotrophic lateral sclerosis

项目摘要/摘要 肌萎缩侧索硬化症(ALS)是一种进行性神经退行性疾病，影响运动神经元 脊髓和大脑。肌萎缩侧索硬化症会导致肌肉无力和瘫痪，最终导致死亡。根据 肌萎缩侧索硬化症协会，每90分钟就有一例新的肌萎缩侧索硬化症诊断，以及一例相关死亡。差一点 每年有5,000人被诊断出患有肌萎缩侧索硬化症，任何时候都至少有16,000人患有这种疾病 仅在美国。FDA批准的治疗肌萎缩侧索硬化症的药物有3种，但这些药物的疗效有限。在……里面 在这个第一阶段的STTR项目中，我们建议进行翻译研究来评估最近开发的一个 ALS模型中的神经元超兴奋性抑制技术。如果成功，目前的影响 该项目是使用无创超兴奋性治疗ALS临床实践中的深远变化 压制。帕特梅克神经系统公司是一家临床阶段的神经调节公司，开发出第一款 基于我们开创性的多路径分布式控制系统，用于治疗严重神经疾病的一流设备 技术，这使得脊髓电路和运动神经元活动的非侵入性调制成为可能。我们的目标 对于这个第一阶段的STTR项目来说，是进行关键的翻译研究，这将是推进这一目标的关键 超兴奋性抑制技术作为一种安全有效的新疗法走向人体临床试验 为肌萎缩侧索硬化症。该项目由三个具体目标组成：在具体目标1中，我们将开发和交付研究用途 多路分布式控制系统设备，便于同时进行动物刺激。在具体目标2中，我们将在最初的基础上展开 转基因ALS小鼠研究以进一步评估多路径DC对生存、运动功能和 兴奋性。在具体目标3中，我们将进行运动神经元计数，以评估多路径分布式控制系统对 运动神经元存活。这些具体目标将有助于生成一系列临床前数据，这些数据将提供 将这项技术转化为人类临床可行性研究的基础。随着我们公司致力于将 突破性的学术研究确定了一种基于以下因素的治疗ALS的新方法 神经元超兴奋性抑制，1期STTR支持将推进这一革命性的治疗选择 即将进行人体临床试验，并将为这项技术在潜在的其他领域的应用铺平道路 运动神经元病。

PROJECT SUMMARY / ABSTRACT Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the spinal cord and brain. ALS causes muscle weakness and paralysis and eventually death. According to the ALS Association, every 90 minutes there is a new diagnosis of ALS, as well as an associated death. Nearly 5,000 people are diagnosed with ALS each year and at least 16,000 are living with the disease at any given time in USA alone. There are 3 FDA-approved drugs for ALS, however, the effectiveness of these drugs is limited. In this Phase 1 STTR project, we propose translational studies to evaluate the effects of a recently developed neuronal hyperexcitability suppression technique in ALS models. If successful, the implications of the current project are far-reaching changes in clinical practice for treating ALS using non-invasive hyperexcitability suppression. PathMaker Neurosystems Inc. is a clinical-stage neuromodulation company developing first-in- class devices for the treatment of serious neurological disorders based upon our pioneering multi-path DCS technology, which enables the non-invasive modulation of spinal circuits and motor neuron activity. Our objective for this Phase 1 STTR project is to conduct key translational studies that will be essential for advancing this hyperexcitability suppression technology towards human clinical trials as a safe and efficacious new treatment for ALS. The project consists of 3 Specific Aims: In Specific Aim 1, we will develop and deliver research-use multi-path DCS devices facilitating concurrent animal stimulations. In Specific Aim 2, we will expand on initial transgenic ALS mouse studies to further assess the effects of multi-path DCS on survival, motor function and excitability. In Specific Aim 3, we will conduct motor neuron counts to assess the effects of multi-path DCS on motor neuron survival. These Specific Aims will help generate a package of pre-clinical data that will provide a basis to move the technology into a human clinical feasibility study. As our company works to translate the groundbreaking academic studies that have identified a novel approach to the treatment of ALS based on neuronal hyperexcitability suppression, Phase 1 STTR support will advance this revolutionary treatment option to the brink of human clinical trials, and will pave the way for application of this technology to potentially other motor neuron diseases.