Shelf-stable, water-soluble prodrugs of progesterone oximes for the treatment of traumatic brain injuries (TBI).
- Compound has activity equal to native progesterone, but is readily soluble in aqueous based, injectable dose formulations and well suited for use in the clinic and by first responders.
- Compound has been shown to cross the blood brain barrier (BBB).
In the United States, an estimated 1.7 million people suffer a traumatic brain injury (TBI) and 52,000 result in deaths annually. Several compounds are being investigated for the treatment of acute TBI, but there is currently no approved pharmacological treatment for TBI. Maintenance of TBI is aimed at minimizing or preventing secondary injury due to TBI and rehabilitation. Progesterone, present in the brains of men and women, has the potential for dramatically improved patient outcome following head trauma.
Researchers at Emory University have shown that progesterone oximes reduce brain edema and functional impairments in rat models of traumatic brain injury and stroke. A series of prodrug derivatives of these oximes have been identified that are sufficiently water soluble and stable in solution to allow for facile formulation for intramuscular or intravenous administration. Pharmacokinetic studies show that the prodrugs are rapidly cleaved in vivo to generate high levels of the active oxime in plasma and in brain tissue. This technology is therefore suitable for use by both first responders and physicians to allow for rapid administration to patients with TBI or stroke.
- Lead compound has been identified.
- In vivo studies have been completed in appropriate animal models.