Amnion cell secretome mediated therapy for traumatic brain injury

Individuals who have sustained a traumatic brain injury (TBI) have emerged as a significant cause of death to the Warfighters in Iraq and Afghanistan. Whether mild, moderate or severe brain injury, the level of assessment and standard of care provided to the Veteran Population is in need of enhancement. To this

end, to expand upon the limited knowledge of the long-term effects of traumatic brain injury, we propose to use our animal model of repetitive-mTBI (r-mTBI) and test a novel treatment to treat/prevent the progression of the chronic pathology following r-mTBI. We hypothesize that a delayed and chronic intranasal treatment with ST266 will mitigate the functional and

neuropathological consequences of r-mTBI by improving, cognition, anxiety, sensory and motor function, and with modulation of neuroinflammation in the CNS and in its periphery. ST266 is a proprietary secretome produced by Noveome Biotherapeutics, Inc that contains hundreds of biologically active proteins and other

factors that have been shown to be crucial to neuroprotection, modulation of inflammation, cell recovery and healing. The overarching aim of the proposed study is to investigate and refine our understanding of the chronic effects of r-mTBI, using our mouse model of r-mTBI. In addition, this project will investigate the

independent association of sex with outcome after r-mTBI with or without treatment with ST266. In the first aim, male and female animals will be exposed to five mTBIs, and then treated daily with a Low or High dose of ST266 delivered intranasally, or saline for a period of 4 months starting at 6 or 18 months

post-last injury. The neurobehavioral performance will then be evaluated at both 10- and 22-months post- injury. In the second aim, neuropathological and biochemical analyses will be evaluated at the same time point. Finally, in the third aim, blood biomarkers associated with neurobehavioral recovery such a BDNF or

other pro-inflammatory cytokines will be evaluated acutely and chronically post r-mTBI and pre and post ST266 treatment. For each aim, we will evaluate the same outcome measures in female and male mice who have undergone our 5-injury paradigm to identify sex-specific differences. We believe these findings

will have broad applicability in TBI research, as the data generated in this study will further the understanding of the complex interaction between ST266 and TBI, and furthermore, we believe this study will provide novel insight into TBI-related pathology and cognitive issues over time in both male and female

Veterans. By assessing nuanced aspects of neurobehavioral and pathological deficits, we will provide a framework from which informed decisions can then be made about the cellular and molecular mechanisms that are most important to target to reduce long term TBI-related pathology, and furthermore, which therapeutic

intervention strategy best suits the patient. Within 30 months from the start date of this project, we will be able to determine: 1) Which delayed treatment if any, provide neurological recovery based on the behavioral and neuropathological outcome markers; and 2) Preclinical success in the study proposed here will enable

Noveome to file an investigational new drug application to conduct a clinical trial specifically addressing this indication which will translate into the improvement of the health or quality of life for Veterans affected by the long-term consequences of r-mTBI.