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

项目概要/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ALS会导致肌肉无力和瘫痪，最终死亡。根据 ALS协会，每90分钟有一个新的ALS诊断，以及相关的死亡。近 每年有5，000人被诊断患有ALS，至少有16，000人在任何特定时间患有这种疾病 仅在美国。有3种FDA批准的药物用于ALS，然而，这些药物的有效性有限。在 这个第一阶段的STTR项目，我们提出了翻译研究，以评估最近开发的一种 在ALS模型中的神经元过度兴奋抑制技术。如果成功，当前的影响 项目是使用非侵入性过度兴奋治疗ALS的临床实践中意义深远的变化 镇压PathMaker神经系统公司是一家临床阶段的神经调节公司， 基于我们开创性的多路径DCS， 该技术能够对脊髓回路和运动神经元活动进行非侵入性调制。我们的目标 对于这个第一阶段的STTR项目是进行关键的转化研究，这将是必不可少的推进这一点 超兴奋抑制技术作为一种安全有效的新治疗方法进入人体临床试验 对于ALS。该项目包括3个具体目标：在具体目标1中，我们将开发和提供研究用途 多路DCS装置，便于同时进行动物刺激。在具体目标2中，我们将扩展初始 转基因ALS小鼠研究，以进一步评估多途径DCS对存活、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，以评估多径DCS对 运动神经元存活率这些特定目标将有助于生成一组临床前数据， 这是将该技术应用于人类临床可行性研究的基础。由于我们公司致力于翻译 开创性的学术研究，已经确定了一种新的方法来治疗ALS的基础上， 神经元过度兴奋抑制，1期STTR支持将推进这一革命性的治疗选择 到人类临床试验的边缘，并将为这项技术应用于潜在的其他领域铺平道路。 运动神经元疾病

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.