RAP as a therapeutic compound for neuronal regeneration after spinal cord injury

DESCRIPTION provided by applicant RAP as a therapeutic compound for neuronal regeneration after spinal cord injury Novoron Bioscience Inc RESEARCH andamp RELATED Other Project Information Project Summary There are an estimated to new cases of spinal cord injury SCI each year and million people in the United States are paralyzed in some form due to SCI Currently there are no clinically available treatments that target the degraded myelin one of the causes of regenerative failure in the central nervous system CNS after SCI LRP was recently identified as a novel receptor of myelin associated inhibitors MAIs the components of degraded myelin responsible for regenerative failure We have shown in vivo that infusion of the LRP antagonist RAP into the injured spinal cord results in attenuation of RhoA the critical neuronal signal involved in extrinsically mediated regenerative failure Direct inhibition of RhoA has been shown to enhance neuronal regeneration after SCI in rodent models and a pan Rho inhibitor has shown evidence of efficacy in humans in exploratory clinical trials However current therapeutics have so far been limited to single dose administration In contrast RAP has been demonstrated to be readily available to the CNS from the peripheral circulation therefore making it amenable to repeated administration over time giving it therapeutic advantages over current pan RhoA inhibitors As beneficial results have already been observed using direct infusion to the injury site we first wish to assess whether peripheral administration of RAP has comparable beneficial effects on the signaling events associated with regenerative failure after SCI To accomplish this an intravenous administration protocol capable of resulting in sufficient levels of RAP in the CNS must first be established We will then perform long term studies week injury course to assess histological regeneration of damaged neurons as well as evaluate the behavioral benefits over time such as improved locomotion increased paw utilization and response to external stimuli in affected extremities We will also evaluate the effects of RAP infusion on immune infiltration and lesion formation As LRP has been shown to be a critical facilitator of myelin mediated neuroregenerative failure we hypothesize that therapeutic application of RAP to block the LRP MAI interaction will result in significant neuronal regeneration after SCI Additionally the unique biological characteristics of RAP such as CNS bioavailability could make it a superior or perhaps combinatorial therapeutic approach to the current pan RhoA inhibitors As such RAP appears to be a high value potential therapeutic for restoring function after acute spinal cord injury This technology s protected by US patent pending US which is currently in process of exclusive license to Novoron Inc from the University of California San Diego PUBLIC HEALTH RELEVANCE RAP as a therapeutic compound for neuronal regeneration after spinal cord injury Novoron Bioscience Inc RESEARCH andamp RELATED Other Project Information Project Narrative There are approximately new cases of spinal cord injury SCI each year in the United States and there are no clinically available treatments capable of restoring the regenerative capacity of neurons in the central nervous system after injury We have shown that LRP is a novel receptor mediating extrinsic neuroregenerative failure and blocking LRP in the injured spinal cord with the LRP antagonist receptor associated protein RAP results in attenuation of the neuronal signaling that leads to regenerative arrest The goal of this work is to further assess the viability of RAP as a biologica compound capable of restoring function and quality of life for patients suffering from SCI and complete the proof of concept work necessary for a phase II application and future pre clinical work needed for IND application