Abstract

Background - Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of many antineoplastic drugs including Vincristine, which is used as a first line treatment in many childhood and adult cancers. - The symptoms of CIPN can become so severe that patients are forced to reduce their dosage or cease chemotherapy altogether, resulting in suboptimal treatment of their cancer. - SRPK1 inhibition has been shown to be associated with pain reduction via alterations in VEGF-A alternative splicing in in vivo models of diabetic neuropathy and traumatic nerve injury. - Additional work by members of our lab has shown that inhibition of SRPK1 by SPHINX31, a novel small molecule therapeutic, attenuates both neurite dieback and neuronal sensitisation in ex vivo models of CIPN. - In a previous pilot study, we demonstrated the induction of Vincristine induced mechanical hyperalgesia in an in vivo rodent model using male C57BL/6 mice (Figure 1). - In the present study, we used this model to investigate the prophylactic potential of SPHINX31, a novel small molecule inhibitor of SRPK1 in the prevention of CIPN