Individualized Closed-Loop Neuromodulation Therapy for Alzheimer's Disease

阿尔茨海默病的个体化闭环神经调节疗法

• 批准号: 10680555
• 负责人: Joan A Camprodon
• 金额: $ 20.64万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680555
• 关键词: Action Potentials; Affect; Algorithms; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer' s disease therapy; American; Amyloid; Amyloid Proteins; Atrophic; Behavior; Biological Markers; Biological Phenomena; Brain; Cephalic; Clinical; Clinical Trials; Cognition; Cognitive; Crossover Design; Data; Development; Devices; Diagnostic Procedure; Disease; Disease model; Electric Stimulation; Electroencephalography; Functional disorder; Future; Home; Human; Immunotherapy; Intervention; Investments; Learning; Light; Magnetic Resonance Imaging; Maps; Measures; Membrane Potentials; Memory; Microglia; Modeling; Molecular; Nature; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurosciences; Pathologic; Patients; Perception; Pharmacology; Phase; Physiologic pulse; Physiological; Physiology; Positron-Emission Tomography; Precision therapeutics; Process; Proteins; Public Health; Reading; Resources; Rest; Rodent; Rodent Model; Role; Safety; Senile Plaques; Sensory; Techniques; Technology; Therapeutic; Therapeutic Intervention; Thick; Translating; Work; biomarker discovery; blind; brain abnormalities; cognitive performance; cost effective; functional outcomes; improved; in vivo; manufacture; mild cognitive impairment; neural; neurophysiology; neuropsychiatry; neuroregulation; novel; portability; recruit; sound; symptom treatment; symptomatic improvement; tau Proteins; therapy development; tool; treatment strategy

PROJECT SUMMARY/ABSTRACT Alzheimer’s Disease (AD) is a neurodegenerative disease that affects over 5 million Americans. Despite its clinical and public health impact, and the resources invested in treatment development, existing therapies remain only symptomatic (not disease modifying) and have modest efficacy. Disease models have traditionally emphasized molecular (maladaptive changes in -amyloid and tau proteins) and cellular (neurodegeneration) processes. Therefore, treatment development has focused on interventions that engage these molecular and cellular mechanisms, i.e. pharmacology and immunotherapy. Recent developments in pathophysiology, biomarker discovery and treatment development have emphasized a physiological approach to AD, with a focus on gamma oscillations as treatment targets. Critically, evidence in rodents suggests that engaging these aberrant physiological signatures with 40 Hz light and sound stimulation not only restores gamma oscillations and improves memory, but it also activates microglia leading to a reduction in amyloid and tau. Hence, this treatment strategy has the potential to be a disease-modifying therapy, which we are lacking in AD. While engaging gamma oscillations with 40Hz light and sound is a viable strategy, using electrical stimulation to modulate an electrical biological phenomenon should have greater impact. Noninvasive device neuromodulation technologies have been used as neuroscience tools to probe and study brain physiology in humans in vivo for decades, and as diagnostic procedures (e.g. TMS for clinical neurophysiology and presurgical mapping) and therapeutic interventions for neuropsychiatric conditions. tACS is very safe, well tolerared, cheap to manufacture and portable, making it a potentially home-based therapy. The capacity of tACS to engage oscillations in the human brain leading to changes in cognition, behavior and perception is established. That said, given the weak intensity of the electrical currents (e.g. 2mA), tACS may not always effectively engage or reduce ongoing oscillation in the brain. A more sophisticated and individualized “smart tACS” approach that uses closed-loop technology by reading the ongoing EEG activity of the patient and applying the stimulation in phase with the ongoing patient-specific brain activity is now technically possible, and showing to have greater impact on brain oscillations. We hypothesize that closed-loop tACS at 40 Hz in patients with AD should be a more effective strategy to engage these abnormal rhythms, and if the results in rodents translate to humans as early evidence suggests, it may become a much needed disease-modifying intervention (or at least a safe and cost-effective symptomatic treatment).

项目概要/摘要 阿尔茨海默病 (AD) 是一种影响超过 500 万美国人的神经退行性疾病。 尽管其对临床和公共卫生产生影响，并且在治疗开发上投入了资源，但现有的 治疗方法仍然只是对症治疗（而不是改变疾病），而且疾病模型的疗效有限。 传统上强调分子（-淀粉样蛋白和 tau 蛋白的适应不良变化）和细胞 因此，治疗开发的重点是参与的干预措施。 这些分子和细胞机制，即药理学和免疫疗法的最新进展。 病理生理学、生物标志物发现和治疗开发都强调生理学方法 至关重要的是，啮齿类动物的证据表明，以伽马振荡为治疗目标。 将这些异常的生理特征与 40 Hz 光和声音刺激结合起来，不仅可以恢复 伽玛振荡并改善记忆力，但它也会激活小胶质细胞，导致淀粉样蛋白和淀粉样蛋白的减少 因此，这种治疗策略有可能成为一种我们所缺乏的疾病缓解疗法。 广告。 虽然用 40Hz 光和声音参与伽马振荡是一种可行的策略，但使用电 刺激来调节电生物现象应该会产生更大的影响。 神经调节技术已被用作神经科学工具来探索和研究大脑生理学 人类体内已有数十年的历史，并作为诊断程序（例如用于临床神经生理学的 TMS 和 术前定位）和神经精神疾病的治疗干预非常安全。 耐受性好、制造成本低且便于携带，使其成为一种潜在的家庭疗法。 tACS 参与人脑振荡，导致认知、行为和感知发生变化 也就是说，鉴于电流强度较弱（例如 2mA），tACS 可能并不总是有效。 有效地参与或减少大脑中持续的振荡。更复杂和个性化的“智能”。 tACS”方法使用闭环技术，通过读取患者正在进行的脑电图活动和 现在在技术上可以与正在进行的患者特定大脑活动同步施加刺激，并且 结果显示对大脑振荡有更大的影响，我们在 40 Hz 下追求闭环 tACS。 AD 患者应该采取更有效的策略来参与这些异常节律，如果结果 正如早期证据表明的那样，啮齿动物可以转化为人类，它可能成为一种急需的疾病缓解方法 干预（或至少是安全且具有成本效益的对症治疗）。