ALCAMENA STEM CELL THERAPEUTICS, LLC — Department of Health and Human Services SBIR Phase I: 105

Description

AbstractModerate and severe TBI can cause significant neuronal death and dysfunctionresulting in cognitive disabilityThe best strategy to restore neurologic function in TBI patients is to preserve existing neurons and to stimulate neurogenesis to replace lost neural tissueMany therapeutics have sought to accomplish these goalsbut none have succeededresulting in a lack of FDA approved treatments for the restoration of cognitive disabilities that result from TBIThe exact cause of failure is not knownbut we do know that brain injury induces secondary cascades that elevate levels of a transcriptional repressor of neural genes known as RESTUpregulation of REST in mature neurons prevents them from functioning properly and eventually ends in their death and increased levels of REST in stem cells and neural progenitor cells prevent them from becoming new neurons or oligodendrocytesPrevious therapeutic strategies as well as current approaches all work upstream of REST and do not account for this transcriptional blockTo address this challengewe have developed a lead biologic that promotes REST degradation and clears the injury induced transcriptional repression of neuronal genesTo engineer this lead biologic into a drug candidate for an Investigational New DrugINDapplication with the FDA we will carry out the following objectivesIOptimize the activitytissue targeting and intracellular transport of our drug candidateIIAssess in vitro efficacy in human induced pluripotent stemiPScellsIIIAssess in vivo efficacy using a rodent model of TBITo accomplish these objectivesAlcamena Stem Cell Therapeutics is collaborating with field leading academic scientists at Johns Hopkins UniversityJHUand the Uniformed Services University of the Health SciencesUSHS DoDCumulativelythese studies will inform us on the degree to which our drug candidate improves neuron and oligodendrocyte regenerationsurvival and cognitive functionAdditionallythe use of both human induced pluripotent stem cells and an in vivo rodent model of brain injury ensure that our results are translatable towards our long term goal of addressing the unmet therapeutic needs of TBI patients NarrativeTraumatic brain injuryTBIcauses significant neuronal death resulting in motor and cognitive disabilityTo dateall targeted therapies to improve neuronal growth and viability in TBI patients have proved ineffectiveTo address this challengewe have developed a biologic that overcomes the obstacles encountered by other approachesa TBI induced brake on neuronal genesOur lead biologic is both neuroprotective and neurogenic and has the potential to restore cognitive functions such as learning and memoryOur approach offers the greatest promise yet for patients who suffer from cognitive disability caused by TBIIn this proposalwe describe our strategy for optimization and nonclinical assessment of our drug candidate