An oral ROCK2-selective inhibitor for treatment of chronic spinal cord injury

Roughlypeople in the United States will suffer a spinal cord injurySCIthis yearFor the vast majority of themthe injury will leave them incapable of walking orif they have suffered a cervical SCIentirely dependent upon others for assistance in all of their activities of daily living from feeding to personal careMore importantlychances of improvement as a result of therapeutic interventions are bleak since there are no approved therapies that enhance functional outcomesThe cost to these individualsand to society as a wholeare quite large as SCI often occurs in adults in their peak earning yearsThe vast majority of therapeutic interventions currently being tested are developed for use in the acute period from hours to days after injuryFor those not fortunate enough to be in the right hospital withinhours of their injurythere are essentially no therapeutic options being explored outside of the surgical standard of careWe are developing a small molecule inhibitor of ROCKBAwhich could be widely availableeven outside of the acute hospital settingBAis a small molecule inhibitor of ROCKwhich shows favorable safety characteristics after repeat administrationis orally availablepenetrates the nervous systemand has good drug like propertiesROCKis a protein kinase that is highly expressed in the central nervous system and is overactivated following spinal cord injuryThe ROCKsignaling pathway is overactivated days to weeks after SCI and as suchtargeting this kinase with BAcould promote recovery if BAwere to be used days to weeks after injuryWe propose to use a rat spinal cord contusion injury model to establish the dose of BAcapable of restoring normal levels of ROCK signaling after oral administrationBased on these resultswe will undertake a proof of concept study for efficacy of the compound in improving functional recovery after thoracic SCIOnce we have investigated acute usewe will establish whether BAcan improve functional outcomes when administered over two different time frames post injurya sub acute time frame and a sub chronic time frameWe will also examine regenerative growth of descending fiber tracts after injury and treatment with BAwith a focus on the tracts that are sources of motor and neuromodulatory controlAdditionallywe will carry out non clinical GLP safety toxicology studies that will be required by FDA prior to first in human studiesOur overall plan is to develop BAas an orally availablepro regenerative treatment for SCI that can be administered for days or weeks after injury to be used in concert with other modalities such as physical therapy to maximize functional outcomes Project Narrative Many thousands of people in the USA suffer spinal cord injuries each yearand many more are already living with a chronic spinal cord injuryMost drugs under development at present are for use in treating spinal cord patients within the first few days after injury and must be administered under carefully controlled circumstances in the hospitalWe are developing an orally administered drug to improve recovery after spinal cord injury that could be taken from days to weeks after injury