680 Multi-functional drug approach for the treatment of brain injury. (1st September 2016)

• Record Type: Journal Article
• Authors: Harel, Adrian; Kvist, Mårten
• Is Part Of: Injury prevention. Volume 22(2016)Supplement 2
• Page Start: A244
• Page End: A244
• Publication Date: 2016-09-01
• Subjects: Traumatic brain injury -- Drug development; Children's accidents -- Prevention -- Periodicals; Accidents -- Prevention -- Periodicals; 617.1
• DOI: 10.1136/injuryprev-2016-042156.680
• Languages: English
• ISSNs: 1353-8047

Abstract

Abstract : Background: Traumatic brain injury (TBI) is one of the main causes of mortality among military personnel, children, young adults and athletes. Medicortex Finland has adopted a novel approach to attenuate secondary damages related to traumatic brain injury and stroke. TBI is manifested by early events and delayed secondary alterations. The latter include: mitochondrial dysfunction, lipid degradation and peroxidation and blood-brain barrier (BBB) disruption. This is followed by raised intracellular calcium influx and activation of proteases, resulting in axonal swelling, disconnection and degeneration. Pro-inflammatory factors are produced and secreted by local and infiltrated immune system cells, promoting the development of the inflammatory process. This series of events results in various neurological deficits. Since the degenerative process is mediated by multiple biological reactions, agents that target a single pathway are ineffective. Method: Medicortex presents a novel family of new chemical entities that cross the BBB, each possessing a penetrating head with a chemical spacer and two or more of the following properties: binding of free metal ions, anti-oxidation, anti-inflammation, and/or anti-bacterial. The lead compounds will be selected according to their solubility, stability and toxicity. In vitro and in vivo studies are conducted in order to explore the efficacy of the molecules as neuroprotective agents under different insults and to attenuate neural damage, utilising animal models of cortical impact brain injury. Results: The first compound, TBI-466, was tested by repeated injection at different concentrations and was found to be safe. Conclusions: Taken together, Medicortex's multi-functional drug agents will target biochemical pathways occurring at different time points post-injury, thereby attenuating and even preventing secondary TBI-associated neurological dysfunction and neuronal cell death.