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

Treatment of Chemotherapy-Induced Peripheral Neuropathy via Genetic Repression of Sodium Channels

通过钠通道的基因抑制治疗化疗引起的周围神经病变

基本信息

批准号：
10384645
负责人：
Fernando Aleman Guillen
金额：
$ 76.67万
依托单位：
NAVEGA THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-10 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10384645
关键词：
Address Adverse effects Affect Analgesics CRISPR/Cas technology Cancer Patient Chemotherapy-induced peripheral neuropathy Clinical Trials Congenital Pain Insensitivity Dependovirus Dose Down-Regulation Drug abuse Epigenetic Process Evaluation Exhibits Family Future Genes Genetic Genome Goals Guide RNA Human Human Cell Line Human Genome Hypersensitivity Intervention Ion Channel Lead Motor Mus Mutation Neurons Nociception Numbness Opioid Organ Pain Pain intensity Pain management Patients Persistent pain Pharmaceutical Preparations Phase Polyneuropathy Population Proteins Quality of life Reagent Regulation Repression Risk Safety Sensory Severities Small Business Innovation Research Grant Sodium Channel Specificity Spinal Ganglia System Testing Therapeutic Toxic effect Variant Zinc Fingers addiction alternative treatment animal safety base cancer pain chemotherapy chronic pain chronic pain patient clinical development design dosage efficacious treatment epigenome epigenomics experience gene therapy improved induced pluripotent stem cell inhibitor/antagonist innovation mouse genome mouse model nonhuman primate novel novel strategies novel therapeutics pain reduction pain relief precision medicine premature response safety study side effect small molecule tool transcriptome sequencing transmission process treatment duration voltage

项目摘要

Project Summary/Abstract The goal of this project is to develop a gene therapy product that relieves chemotherapy-induced peripheral neuropathy (CIPN) in a non-permanent, non-addictive and long-lasting manner to improve the quality of life of cancer patients. Current management of CIPN and cancer pain is very poor, with 1 in 3 patients not receiving pain medication considered appropriate for the intensity of pain experienced. With the limited efficacious treatment options available, opioids are often prescribed, however these can lead to addiction. We are in urgent need of novel pain therapies that would alleviate the side effects of opioids. Voltage- gated sodium channels (NaV family) have been used in nociceptive transmission and contribution to the hyperexcitability in primary afferent nociceptive neurons. Additionally, many chemotherapy agents induce ion channel expression including NaV1.7 and NaV1.8, leading to CIPN. Hence, these sodium channels have been attractive targets for developing chronic pain therapies. However, the high homology of human NaV proteins has frustrated most efforts to develop selective protein inhibitors. Instead of targeting the protein, Navega proposes to develop a non-permanent epigenome regulation tool to target pain. This novel approach is non-addictive, highly specific, and long-lasting. During Phase I, we determined that the simultaneous inhibition of NaV1.7 and NaV1.8, was more efficacious at reversing CIPN than repressing each channel alone. We also demonstrated the safety of our approach at doses tested in mice. During Phase II we will: 1) perform dose-range studies in mice to determine the therapeutic window; 2) optimize our reagents to target the human genome; and 3) perform GLP definitive safety studies in NHPs. We will prepare an IND application to the FDA, and will submit it at the end of the Phase II project. Our final goal is to develop novel therapeutics that can mitigate CIPN through the use of a specific gene therapy approach that can simultaneously target two voltage gated sodium channels (something not possible with small molecules) and provide an alternative treatment to opioids for patients with chronic pain.

项目总结/文摘