Neurotoxicity Models for Cancer Studies
Charles River has two in vivo models of the neurotoxic effects associated with chemotherapy and many other cancer treatments; peripheral neurotoxicity model and the neuropathic pain model.
Peripheral Neurotoxicity Model
Peripheral neurotoxicity occurs in approximately 40 percent of previously untreated cancer patients who receive chemotherapy regimens containing taxane. Because the effects of this therapy may limit treatment for a significant percentage of patients, it is essential for researchers to have access to study models that can mimic clinical taxane toxicity, and that permit evaluation of the interaction of proposed protectant strategies with the disease and its treatment.
Charles River conducts contract studies in an established animal neurotoxicity model to test the efficacy of novel therapeutics. Readouts include analysis of brain tissue and sciatic nerve, bodyweight measurements, drug response, histology, peripheral nerve evaluation and clinical evaluations.
Bodyweight in Neurotoxicity Model
Effect of maximum tolerated dose of docetaxel on body weight in the mouse model (Relative body weight values for each strain reflect the percent change of the group body weight mean on the day indicated when compared to the mean body weight for day 1.)
Neuropathic Pain Model
In addition to traditional neurotoxicity models, Charles River has a chemotherapy-induced model of neuropathic pain. This chemotherapy-induced polyneuropathy (CIPN) model is induced by chemotherapeutics such as oxaliplatin and involves the development of peripheral polyneuropathy. Oxaliplatin is injected into mice (6 injections of 4.5 mg/kg Oxp) over a period of 21 days and the mice develop cool allodynia that can be quantified with tail immersion test or acetone droplet test.
Looking for safety assessment services? See our Neurotoxicology page.
Frequently Asked Questions (FAQs) for Neurotoxicity Models
Can I test the effects of chemotherapy in a mouse model of neurotoxicity?
Previous neurotoxicity studies in rodent models have focused more on cisplatin than on taxanes, especially docetaxel, and these studies have focused more on rats than on mice. Although selected transplantable tumors may be propagated or studied in rats, the mouse is a more widely used host than the rat for efficacy studies of new cancer therapies. Docetaxel-induced neurotoxicity in mice, which is qualitatively and quantitatively similar to that observed in rats, permits assessment of both toxicity and efficacy in a single model. This is especially useful for evaluating new taxanes, chemoprotective strategies, or other potentially neurotoxic drugs or combinations.
Why is chemotherapy-induced polyneuropathy a relevant model for oncology neurotoxicity?
Oxaliplatin is an effective and widely used first-line chemotherapeutic agent to treat cancer, but a major side effect is the development of peripheral polyneuropathy. In our neurotoxicity models, we can test whether the therapeutic agent reduces chemotherapy-induced pain and/or whether new chemotherapies induce neuropathic pain. This acts as an important complementary model to traditional cancer in vivo models and can be useful for combination studies.
Why should I test my anti-cancer therapeutic in a neurotoxicity model?
A common side effect of chemotherapy, neurotoxicity frequently limits the dose of chemotherapy. Chemotherapy can cause both peripheral neurotoxicity and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. Therefore, it is important to test treatments targeting chemotherapy side effects, including combination therapies, in neurotoxicity models.
Can neurotoxicity models support my CAR-T studies?
Neurotoxicity is a common side effect of CAR-T cell therapies; acute neurological symptoms occur in a significant percentage of patients treated with CD19-directed CAR-T cells for B cell malignancies. Neurotoxicity is associated with cytokine release syndrome seen in in vivo CAR-T cell activation and proliferation. Charles River’s neurotoxicity models can therefore support our other CAR-T cell and oncology cell therapies support services.