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. Public Health Relevance Statement PROJECT NARRATIVE Approximately 450,000 cancer patients in the United States suffer from chemotherapy-induced peripheral neuropathy, a condition of nerve damage leading to symptoms like numbness, tingling, temperature sensitivity, and pain in the hands and feet. This condition poses a significant burden on the patientÂ’s quality of life and the health care system. To date, there are no treatments available. Avantyx Pharmaceuticals will tackle this problem and analyze a newly identified compound targeting the Matrix-Metalloproteinase 13 for the treatment of this condition.
Project Terms: Oral Administration ; Oral Drug Administration ; intraoral drug delivery ; Analgesics ; Analgesic Agents ; Analgesic Drugs ; Analgesic Preparation ; Anodynes ; Antinociceptive Agents ; Antinociceptive Drugs ; pain killer ; pain medication ; pain reliever ; painkiller ; Animals ; inhibitor/antagonist ; inhibitor ; Animal Behavior ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biological Availability ; Bioavailability ; Biologic Availability ; Physiologic Availability ; Collagen ; Diabetic Neuropathies ; diabetes-associated neuropathy ; Pharmacotherapy ; Drug Therapy ; drug treatment ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Enzyme Precursors ; Proenzymes ; Zymogens ; Epidermis ; foot ; Future ; Patient Care ; Patient Care Delivery ; Goals ; Hand ; Healthcare Systems ; Health Care Systems ; Heart ; Hypersensitivity ; Allergy ; Kidney ; Kidney Urinary System ; renal ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Liver ; hepatic body system ; hepatic organ system ; Long-Term Care ; extended care ; longterm care ; Lung ; Lung Respiratory System ; pulmonary ; Mus ; Mice ; Mice Mammals ; Murine ; New England ; Northeastern United States ; Numbness ; Loss of Sensation ; Pain ; Painful ; Pain Measurement ; Analgesia Tests ; Nociception Tests ; Pain Assessment ; pain assay ; Paresthesia ; Veterinary Pathology ; Patients ; Peripheral Nervous System Diseases ; PNS Diseases ; Peripheral Nerve Diseases ; Peripheral Nervous System Disorders ; Peripheral Neuropathy ; Drug Kinetics ; Pharmacokinetics ; Pharmacology ; Phenotype ; Publishing ; Quality of life ; QOL ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Research ; Rest ; Sampling Studies ; Solubility ; Specificity ; Spleen ; Spleen Reticuloendothelial System ; Temperature ; Testing ; Tissues ; Body Tissues ; Toxicology ; United States ; Universities ; Up-Regulation ; Upregulation ; Work ; Zebrafish ; Brachydanio rerio ; Danio rerio ; Zebra Danio ; Zebra Fish ; Health Care Costs ; Health Costs ; Healthcare Costs ; Sensory Nerve Endings ; Paclitaxel ; Anzatax ; Asotax ; Bristaxol ; Paclitaxel (Taxol) ; Praxel ; Taxol ; Taxol A ; Taxol Konzentrat ; sensory neuropathy ; Peripheral Sensory Neuropathy ; Muscle Weakness ; Muscular Weakness ; Acute Pain ; Clinical ; Phase ; Biochemical ; Dermal ; Individual ; collagenase 3 ; MMP-13 ; MMP-13 gene product ; MMP13 gene product ; matrix metalloproteinase-13 ; Rivers ; mechanical ; Mechanics ; Oral ; neuropathic ; Neuropathy ; Sensory ; Route ; allodynia ; Services ; experience ; sensory mechanism ; tumor growth ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Toxicities ; Toxic effect ; novel ; Topical Drug Administration ; administer topically ; apply topically ; deliver topically ; topical administration ; topical delivery ; topical drug application ; topical treatment ; topically administered ; topically applied ; topically delivered ; topically treated ; treat topically ; Topical application ; Drug Interactions ; Prevention ; Modeling ; Property ; drug development ; Cancer Treatment ; Malignant Neoplasm Therapy ; Malignant Neoplasm Treatment ; anti-cancer therapy ; anticancer therapy ; cancer-directed therapy ; cancer therapy ; Skin ; Molecular Interaction ; Binding ; Pharmaceutical Agent ; Pharmaceuticals ; Pharmacological Substance ; Pharmacologic Substance ; Mechanical Stimulation ; preventing ; prevent ; Dose ; Tumor Load ; Tumor Burden ; Symptoms ; Absorption, Distribution, Metabolism, and Excretion Study ; ADME Study ; Inhibition of Matrix Metalloproteinases ; Inhibition of Matrix Metalloproteinases Pathway ; NCI Organization ; National Cancer Institute ; in vivo ; in vivo Model ; Cancer Patient ; Cancer Survivor ; survive cancer ; Extracellular Matrix Degradation ; Rodent Model ; Scheme ; axon regeneration ; axonal regeneration ; Topical agent ; axonal degeneration ; axon degeneration ; degenerative axon ; efficacy evaluation ; efficacy analysis ; efficacy assessment ; efficacy examination ; evaluate efficacy ; examine efficacy ; innovation ; innovate ; innovative ; chemotherapy ; drug candidate ; phase 1 study ; Phase I Study ; Chemotherapy-induced peripheral neuropathy ; targeted agent ; efficacy study ; therapeutic candidate ; Injections ; nerve damage ;
