Synthetic Analogues of Progesterone

Emory University
posted on 06/09/2011

Applications

Therapeutic treatment of traumatic brain injury and other uses of progesterone where composition of matter intellectual property are required.

Highlights

20 fold increase in solubility relative to the hormone progesterone.
Synthetic analogues are as effective as progesterone in reducing cerebral edema following traumatic brain injury.

Technical Summary

Traumatic brain injury (TBI) occurs in 1.4 million members of the U.S. population per year, resulting in more than 50,000 deaths annually and significant long-term neuronal damage in many of those affected. To date, progesterone is the only therapeutic agent that has demonstrated reproducible clinical benefits in the hospital setting to patients suffering from moderate to severe TBI. The hormone is now in Phase III testing as a treatment for moderate to severe TBI. Progesterone therapy addresses multiple processes in the secondary injury cascade, providing neuroprotection against both acute and long-term effects of a TBI. However, it is has limited emergency use due to its negligible water solubility and short plasma half-life. Therefore, a second-generation version of progesterone is needed in an emergency setting formulation that can be administered quickly via a syringe-compatible injection with prolonged serum half-life.

Investigators at Emory University have identified a set of stable, water-soluble progesterone prodrugs and analogs that retain the therapeutic properties of progesterone, while allowing rapid administration in emergency situations. Pharmacokinetic studies have revealed that many of these compounds exhibit a half-life in vivo that is significantly longer than that of progesterone, allowing prolonged exposure for greater therapeutic benefit.