Therapeutic Targets for Traumatic Brain Injury
Categories: “Neurodegenerative Therapeutics“
Reference #: 2008-003
OTC Contact: David Humphrey, Ph.D. (Directory Information | Send a Message)
Georgetown University is seeking a licensing partner interested in the development of therapeutic treatments for traumatic brain injury (TBI). TBI is the leading cause of mortality and disability among young individuals in developed countries. Currently, there is no effective treatment for patients following TBI. The initial injury induces biochemical and cellular changes that contribute to continuing neuronal damage and death over time. This continuing damage is known as secondary injury. Post mortem studies have shown that 30% of TBI fatalities have amyloid-beta deposits, which may occur less than 1 day post injury. Georgetown researchers have shown in a recent Nature Medicine paper that blocking either beta- or gamma-secretase, proteins responsible for amyloid-beta production, can dramatically reduce motor and cognitive defects and reduce cell loss after experimental TBI.
This technology encompasses a new therapeutic approach for the treatment of traumatic brain injury. It represents a potential breakthrough in treating patients suffering from TBI and may greatly reduce or prevent the long term neuronal damage from secondary injury.
Treatment with amyloid precursor protein secretase inhibitors dramatically decreases motor loss and cognitive deficits that are commonly associated with experimental TBI. In addition, administration of these inhibitors diminishes the effects of secondary injury from TBI by reducing brain cell loss due to necrosis and apoptosis.
Stage of Development
Mice were subjected to a controlled cortical impact as an experimental model of TBI. Functionally, this model of TBI results in deficits of fine motor coordination (as evidenced by a beam walk test), and hippocampal deficits with reduced spatial learning in a Morris water maze test. MRI assessment of the damage showed extensive lesions spreading from the cortex through the hippocampus and connecting to the lateral ventricles. However, injured mice lacking beta-secretase (Bace1-/-) lost less than 7% of hippocampal tissue compared to 65% loss for mice containing beta-secretase (Bace1+/+). Pharmacological inhibition of gamma-secretase also reduces post-traumatic tissue loss and improves cognitive and motor recovery after trauma. Since the gamma-secretase inhibitor was administered after trauma, it models a clinically relevant situation.
“Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury.” Nature Medicine. 2009,15 (4), 377-379.
Patents are currently pending.