权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Kv2.1-Targeted First in Class Neuroprotective Therapeutic for Acute Ischemic Stroke

Kv2.1 靶向急性缺血性中风的一流神经保护疗法

基本信息

批准号：
10598185
负责人：
Julie H Coleman
金额：
$ 23.2万
依托单位：
CELDARA MEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598185
关键词：
Acceleration Acute Adverse effects Alteplase Alzheimer&apos s Disease American Animal Model Animals Brain Infarction Cell Death Cell Death Induction Chronic Climacteric Clinical Cytoplasm Data Development Dose Eligibility Determination FDA approved Fibrinolytic Agents Freezing Frequencies Funding Goals Guidelines Health Industry Infarction Intervention Investments Ischemia Ischemic Penumbra Ischemic Stroke Kv2.1 channel Laboratories Lead Maximum Tolerated Dose Measures Mechanics Middle Cerebral Artery Occlusion Modeling National Institute of Neurological Disorders and Stroke Nerve Degeneration Neurologic Neurological status Neurons Neuroprotective Agents Outcome Pathway interactions Patients Persons Pharmaceutical Preparations Phase Potassium Potassium Channel Blockers Pre-Clinical Model Production Program Development Radiology Specialty Rattus Reproducibility Rodent Rodent Model Salvage Therapy Signal Pathway Signal Transduction Solubility Stroke Therapeutic Thrombectomy Time Toxic effect Translating Traumatic Brain Injury Validation Work aged cerebrovascular clinically relevant delayed rectifier potassium channel disability disability-adjusted life years economic cost economic impact efficacy study follow-up improved improved outcome in vitro activity ischemic injury mouse model multidisciplinary nervous system disorder neuron apoptosis neuron loss neuroprotection novel patient population phase 1 study pre-clinical pre-clinical assessment preservation prevent programs response side effect stroke model stroke patient stroke therapy

项目摘要

Project Summary Acute ischemic stroke (AIS) impacts 795,000 Americans per year, leaving 90% of patients with chronic disability. Prevalent cases of AIS in the US were estimated at 6.7M in 2017, translating to 6M Americans living with permanent stroke-related disability. AIS is characterized by cerebrovascular blockage that results in the formation of a central infarct with a surrounding ischemic penumbra; the goal for neuroprotection is based on the fundamental concept of penumbral preservation (a.k.a. penumbral freezing). Currently, the only approved therapy for patients suffering from AIS is the thrombolytic agent alteplase (tPA), approved in 1996 and burdened by expansive side effects, a host of contraindications restricting eligible patient populations, and a limited therapeutic time window. Importantly, the use of mechanical thrombectomy has drastically increased in the past decade, bringing along improved clinical outcomes. It has been strongly argued that thrombectomy outcomes can be further improved by neuroprotective therapies that salvage neuronal loss in the penumbra. Our team has identified a signaling pathway that is ubiquitously activated following ischemic injury, enabling the completion of neuronal programmed cell death. Our lead neuroprotective, CM-EA1, specifically disrupts this neuronal cell death pathway. CM-EA1 is being developed to treat patients suffering from AIS, to prevent neuronal loss in the ischemic penumbra, translating to decreased disability-adjusted life years (DALYs) for patient suffering from AIS. In this application, we will demonstrate efficacy via a rigorous rat transient middle cerebral artery occlusion (tMCAO) dose-escalation study. Following these key efficacy studies, we will advance CM-EA1 to aged rodent models and large gyrencephalic animals in a Phase II development program. Our multidisciplinary team brings together a unique combination of academic, clinical and commercial expertise that will permit the development of a life-changing drug for AIS patients.

项目总结