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Reversal of preexisting neuropathic pain by spinal delivery of AIBP

通过脊髓输送 AIBP 逆转先前存在的神经性疼痛

基本信息

批准号：
10197482
负责人：
Yury Miller
金额：
$ 37.67万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10197482
关键词：
Affect Agonist American Animal Model Animals Anticonvulsants Antiinflammatory Effect Apolipoprotein A-I Astrocytes Behavioral Assay Binding Proteins Biological Biological Assay Biological Response Modifier Therapy Biological Sciences Blood - brain barrier anatomy Blood specimen Bortezomib Burning Pain California Cell membrane Cellular Membrane Chemicals Chemotherapy-induced peripheral neuropathy Cholesterol Chronic Cisplatin Clinical Collaborations Dependence Development Diabetes Mellitus Dimerization Dose Drug Kinetics Esthesia Excision Formulation Future Goals Harvest Hyperalgesia Inflammation Inflammatory Injections Injury Laboratories Lead Ligation Measurement Mediating Medical Membrane Microdomains Microglia Mononeuropathies Mus National Institute of Neurological Disorders and Stroke Nerve Neuroglia Neuropathy Non-Steroidal Anti-Inflammatory Agents Oncology Opioid Pain Peripheral Nerves Peripheral nerve injury Persistent pain Pharmacodynamics Phase Phenotype Polyneuropathy Prevention Production Protein Chemistry Proteins Protocols documentation Quality of life Regulation Research Research Design Resolution Route Sensory Spinal Spinal Cord Spine pain Stimulus Symptoms TLR4 gene Tactile Testing Therapeutic Therapeutic Equivalency Tissues Translating Trauma Universities Virus Diseases Work addiction allodynia base brain tissue chemotherapeutic agent chemotherapy chronic pain clinical development conditioned place preference cytokine design epigen glial activation human model immune activation in vitro Assay manufacturing process manufacturing scale-up mouse model nerve injury neuroinflammation novel novel strategies pain relief painful neuropathy pharmacokinetics and pharmacodynamics preclinical development programs receptor function research clinical testing response side effect

项目摘要

Project Summary Peripheral nerve injury can lead to anomalous sensations referred to as neuropathic pain. Nerve injury may result from a variety of insults ranging from frank injury to the nerve though sectioning or compression, and is particularly prevalent following chemotherapies used in oncology. Symptoms often include continuous burning pain and abnormal sensory sensations such as allodynia (pain as a result of non-noxious stimuli) and hyperalgesia (an increased response to a normally painful stimulus) Persistent pain after resolution of clinically appreciable signs of injury poses a therapeutic challenge and current therapies do not meet this medical need. Accordingly, novel treatment options that afford additional benefit in prevention or relief of pain are needed. In this proposal, a collaboration initiated between the University of California San Diego (UCSD) and Epigen Biosciences Inc. seeks to fully evaluate the apoA-I binding protein (AIBP), an agent that interferes with inflamed lipid rafts in spinal glia and has been found to reverse facilitated pain states in several mouse models. The goals of this proposal during the R21 phase include the AIBP protein manufacture and characterization, pharmacokinetics studies, design and refinement of experimental animal protocols to assess efficacy and pharmacodynamics of AIBP in mouse models of polyneuropathy (induced by chemotherapeutic agents) and mononeuropathy (L5 nerve ligation), and optimization of pharmacodynamics assays to evaluate AIBP engagement of spinal glia and its anti-inflammatory effects. Contingent upon the successful completion of a set of proposed milestones, the R33 phase will commence to establish dose-dependent efficacy profile for AIBP treatment of neuropathic pain and to correlate it with AIBP pharmacokinetics and pharmacodynamics. The proposal is designed to advance the AIBP project to the point where it can meet the entry criteria for NINDS Cooperative Research to Enable and Advance Translational Enterprises (CREATE) program, with the ultimate goal to develop a novel biologic therapeutics for management of persistent pain states.

项目总结