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

多路径 DCS 作为肌萎缩侧索硬化症的新型非侵入性治疗方法

• 批准号: 10384856
• 负责人: Zaghloul Ahmed
• 金额: $ 37.16万
• 依托单位: PATHMAKER NEUROSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384856
• 关键词: ALS pathology; ALS patients; Affect; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Anodes; Bilateral; Blood flow; Brain; Brain-Derived Neurotrophic Factor; Cathodes; Cessation of life; Characteristics; Chronic; Clinical; Clinical Data; Clinical Trials; Cohort Studies; Data; Development; Devices; Diagnosis; Disease; Disease Progression; Effectiveness; Electrodes; Electrophysiology (science); FDA approved; Feasibility Studies; Funding; Goals; Growth Factor; Heat shock proteins; Heat-Shock Proteins 70; Human; Impairment; Lead; Methods; Modality; Modeling; Molecular; Motor; Motor Neuron Disease; Motor Neurons; Mus; Muscle; Muscle Weakness; Na(+)-K(+)-Exchanging ATPase; Neural Pathways; Neurodegenerative Disorders; Neurons; Paralysed; Pathologic; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Physiological; Placebos; Potassium Chloride; Preparation; Prophylactic treatment; Pump; Reporting; Research; Research Personnel; Rodent; Small Business Technology Transfer Research; Sodium; Source; Spinal; Spinal Cord; Techniques; Technology; Testing; Therapeutic; Therapeutic Uses; Time; Tissues; Transgenic Mice; Transgenic Organisms; Translating; United States; United States National Institutes of Health; Validation; Vascular Endothelial Growth Factors; Work; active method; amyotrophic lateral sclerosis therapy; base; clinical development; clinical practice; cost; density; design; efficacy evaluation; improved; motor disorder; mouse model; nervous system disorder; neuronal excitability; neuroregulation; novel; novel strategies; pre-clinical; programs; protective effect; spasticity; spinal pathway; success; superoxide dismutase 1; symporter; translational study

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.

项目摘要 /摘要 肌萎缩性外侧硬化症（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引起肌肉无力和麻痹，并最终死亡。根据 ALS协会，每90分钟就会有一个新的ALS诊断，以及相关的死亡。几乎 在任何给定时间 仅在美国。 ALS有3种FDA批准的药物，但是，这些药物的有效性受到限制。在 该阶段1 STTR项目，我们提出了翻译研究，以评估最近开发的效果 ALS模型中的神经元过度抑制技术。如果成功，当前的含义 项目是使用非侵入性过度克服治疗ALS的临床实践的深远变化 抑制。 Pathmaker Neurosystems Inc.是一家临床阶段的神经调节公司 基于我们的开拓性多路径DC治疗严重神经系统疾病的类设备 技术，可实现脊柱电路和运动神经元活动的无创调节。我们的目标 对于这个阶段1的STTR项目是进行关键的转化研究，这对于推进这一点至关重要 过度刺激性抑制技术针对人类临床试验，作为一种安全有效的新治疗 对于ALS。该项目由3个特定目的组成：在特定目标1中，我们将开发和提供研究利用 多路径DCS设备促进并发动物刺激。在特定的目标2中，我们将扩展初始 转基因ALS小鼠研究，以进一步评估多路径DC对生存，运动功能和 兴奋性。在特定目标3中，我们将进行运动神经元计数以评估多路径DC对 运动神经元生存。这些具体目的将有助于生成一套临床前数据，该数据将提供一个 将技术转移到人类的临床可行性研究中。当我们公司努力翻译 开创性的学术研究已经确定了一种基于ALS治疗的新方法 神经元过度抑制性抑制，第1阶段的STTR支持将推进这种革命性的治疗选择 面向人类临床试验的边缘，并将为将该技术应用于其他可能的其他方式铺平道路 运动神经元疾病。