Analyzing the efficacy of MMP-13 inhibitors in the treatment of CIPN

MMP-13抑制剂治疗CIPN的疗效分析

基本信息

批准号：
10323774
负责人：
Sandra Rieger
金额：
$ 35.57万
依托单位：
AVANTYX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-08 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323774
关键词：
ADME Study Acute Pain Analgesics Animal Behavior Animal Model Animals Binding Biochemical Biological Assay Biological Availability Cancer Patient Cancer Survivor Chemotherapy-induced peripheral neuropathy Clinical Collagen Dermal Diabetic Neuropathies Dose Drug Interactions Drug Kinetics Enzyme Precursors Epidermis Extracellular Matrix Degradation Future Goals Hand Health Care Costs Healthcare Systems Heart Hypersensitivity Individual Inhibition of Matrix Metalloproteinases Pathway Injections Kidney Laboratories Lead Liver Long-Term Care Lung Mechanical Stimulation Mechanics Modeling Mus Muscle Weakness National Cancer Institute Neuropathy New England Numbness Oral Oral Administration Paclitaxel Pain Pain Measurement Paresthesia Patient Care Patients Peripheral Nervous System Diseases Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Phase Phenotype Prevention Property Publishing Quality of life Rattus Research Rest Rivers Rodent Model Route Sampling Studies Scheme Sensory Sensory Nerve Endings Services Skin Solubility Specificity Spleen Symptoms Temperature Testing Tissues Topical agent Topical application Toxic effect Toxicology Tumor Burden United States Universities Up-Regulation Veterinary Pathology Work Zebrafish allodynia axon regeneration axonal degeneration cancer therapy chemotherapy collagenase 3 drug candidate drug development efficacy evaluation efficacy study experience foot in vivo in vivo Model inhibitor/antagonist innovation nerve damage novel phase 1 study prevent sensory mechanism sensory neuropathy targeted agent therapeutic candidate tumor growth

项目摘要

Project Summary The goal of this project is to establish an effective drug candidate to treat chemotherapy-induced peripheral neuropathy (CIPN). The National Cancer Institute estimates that approximately 400,000 (or ~60-70%) of patients undergoing chemotherapy suffer from CIPN. These patients may need to terminate chemotherapy treatment if experiencing symptoms, such as numbness, pain, temperature sensitivity, or tingling. Cancer survivors furthermore often have to live with CIPN for the rest of their lives. To date are no treatments available with which to tackle this problem. CIPN costs the healthcare system upward of $13B annually for long-term care of the patients. Thus, there is a significant clinical and economical need to develop drug therapies. Avantyx Pharmaceuticals, LLC has identified a new compound targeting the Matrix-Metalloproteinase 13 (MMP-13), which was shown to promote the degeneration of sensory nerve endings in animal models for CIPN induced by paclitaxel treatment. The key focus of this Phase I project is to characterize a novel MMP-13 inhibitor for its bioavailability, efficacy, specificity, and toxicity in a rat model of paclitaxel-induced peripheral neuropathy, which is following studies in which we established the efficacy of this inhibitor in zebrafish. Key goals are to establish parameters, such as optimal route of administration (oral or topical), optimal dosing, and target specificity, which is necessary to proceed to further drug development studies in Phase II.

项目概要该项目的目标是建立一种有效的候选药物来治疗化疗引起的外周血神经病（CIPN）。美国国家癌症研究所估计，大约 400,000（或约 60-70%）的接受化疗的患者患有 CIPN。这些患者可能需要终止化疗如果出现麻木、疼痛、温度敏感或刺痛等症状，请进行治疗。癌症此外，幸存者往往不得不在 CIPN 中度过余生。迄今为止尚无可用的治疗方法来解决这个问题。 CIPN 每年使医疗保健系统花费超过 $13B 的长期费用照顾病人。因此，开发药物疗法具有显着的临床和经济需求。 Avantyx Pharmaceuticals, LLC 发现了一种针对基质金属蛋白酶 13 的新化合物 (MMP-13)，在 CIPN 动物模型中显示可促进感觉神经末梢变性由紫杉醇治疗引起。该第一阶段项目的重点是表征新型 MMP-13 抑制剂在紫杉醇诱导的外周血大鼠模型中的生物利用度、功效、特异性和毒性神经病变，这是在我们确定这种抑制剂对斑马鱼的功效的研究之后进行的。钥匙目标是建立参数，例如最佳给药途径（口服或局部）、最佳剂量和目标特异性，这是进行第二阶段进一步药物开发研究所必需的。