Peripheral Neuropathy

Peripheral neuropathies (PN) are common and debilitating disorders of various origin (metabolic -e.g. diabetes, toxic – e.g. chemotherapy, or genetic).   Biomodels offers rodent models of PN for the assessment of safety and efficacy of investigational compounds. 

Electrophysiological nerve conduction measurements (or neurography) are non-invasive tools considered the “gold standard” for determining early changes in motor and sensory nerve function that can be applied to the characterizations of all peripheral neuropathies or to assess the effects of neuroprotective agents.   A decrease in nerve conduction velocity (NCV) is usually seen with all neuropathies, regardless of their origin.   Additional behavioral and histopathological endpoints are added and customized based on the compound studied.

Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Peripheral neurotoxicity is a disabling clinical adverse effect of chemotherapeutic drugs, frequently evolving after a single drug application and resulting in damage to the neuronal cell body, the axonal transport system, the myelin sheath, or the glial support structures.  CIPN is dose limiting and often severely impairs the quality of the patient’s life.   As most therapeutic approaches are restricted to symptomatic treatment of paraesthesia and pain, effective neuroprotective strategies to prevent or minimize the symptoms are a current focus of research in CIPN.

Relevant preclinical animal models are key in the development of neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.  As the causes of neurotoxicity can be complex and dependent on the type of compound, preclinical models need to be flexible in capturing key biomarkers of function common to all chemotherapeutic agents.  Biomodels’ approach to testing effects of chemotherapeutics or neuroprotective agents involves the longitudinal assessment of electrophysiological functional endpoints common to all types of CIPN.

Electrophysiological nerve conduction measurements (or neurography) are non-invasive tools considered the “gold standard” for determining early changes in motor and sensory nerve function that can be applied to the characterizations of all peripheral neuropathies or to assess the effects of neuroprotective agents.  A decrease in nerve conduction velocity (NCV) is usually seen with all classes of chemotherapeutic drugs.   Additional behavioral and histopathological endpoints can be added and customized based on the compound studied and the scientific question being asked.

Study Design Table 

Model Description Duration In-Life Analyses
Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Peripheral neuropathy is induced by treatment with cisplatin or other chemotherapy in rats or mice

8-12 weeks; variable recovery Nerve Conduction, Behavioral endpoints

 

Diabetes-Induced Peripheral Neuropathy (DPN)

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, characterized by progressive, distal-to-proximal degeneration of peripheral nerves leading to pain, weakness, and sensory impairment.  

Relevant preclinical animal models of type 1 (T1DM) and type 2 diabetes (T2DM) are key in the development of neuroprotective strategies and in the design of novel therapies with improved toxicity profiles. Biomodels’ approach to testing effects of therapeutic agents involves the longitudinal assessment of electrophysiological functional endpoints common to all types of DPN.

As a decrease in nerve conduction velocity (NCV) is usually seen with type I and type II diabetes, non-invasive tools electrophysiological nerve conduction measurements (or neurography) can be used  longitudinally for determining early changes in motor and sensory nerve function or to assess the effects of neuroprotective agents  Additional behavioral and histopathological endpoints can be added and customized based on the compound studied and the scientific question being asked.

Study Design Table

Model Description Duration In-Life Analyses
Streptozotocin-induced diabetes in rats and mice Peripheral neuropathy can be detected starting 4-8 weeks after treatment 8-12 weeks; variable recovery Nerve conduction, Behavioral endpoints, Body weight, Glucose test

Genetic Diabetes in Zucker and ZDF rats, ob/ob and db/db mice

Peripheral neuropathy is present at baseline and evolves over 4-8 weeks, as the disease progresses  4-8 weeks; variable recovery

 

Streptozotocin-induced Diabetic Rats Blood Glucose Levels (Days 37 and 65)
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