Mitigating Taxol-Induced Neuropathy through Modulation of the NMDA Receptor

DESCRIPTION provided by applicant Taxol paclitaxel is the one of the most widely used chemotherapy agents and is a first line treatment for ovarian breast lung and colon cancer Despite its well documented anti cancer properties taxol is known to cause chemotherapy induced peripheral neuropathy CIPN CIPN affects approximately of all chemotherapy patients and the neuropathic pain can be so severe that in some cases chemotherapy treatments must be discontinued Therapeutic options for patients with CIPN are currently very limited and so a new approach for mitigating the effects of CIPN could have a significant clinical impact Naurex is investigating a new approach to addressing CIPN The company has developed a novel class of non toxic orally bioavailable compounds that modulate the N methyl D aspartate receptor NMDAR within the glutamatergic system The NMDAR is involved in regulation of synaptic plasticity and it is known that neuropathic pain results in the dysregulation of synaptic plasticity Our preliminary data shows that Naurexandapos s NMDAR partial agonists display a dose dependent analgesic effect in a rat Taxol model of CIPN A lead compound NRX was identified from these initial studies that displays desirable pharmaceutical properties in addition to excellent activity in the rat Taxol model The scope of this Phase I SBIR project is to conduct pre clinical studies to further evaluate the therapeutic potential of NRX for mitigating CIPN To this end our Specific Aims are Aim Establish dose response of NRX Aim Evaluate NRX andapos s therapeutic potential for prevention and treatment of CIPN Aim Evaluate pharmacokinetics and toxicity of NRX in combination with Taxol Successful completion of this Phase I project will establish effective dosing regimens of NRX that will inform follow on IND enabling studies as well as clinical trial protocols Given the widespread use of taxol and its proven effectiveness as a chemotherapeutic agent the potential to reduce the main side effect associated with its usage would be highly significant in the field of oncology PUBLIC HEALTH RELEVANCE Taxol is one of the most widely used chemotherapeutic agents for treating cancer One of the most common side effects associated with taxol is chemotherapy induced peripheral neuropathy CIPN This project will evaluate a new approach to preventing and or treating CIPN