Analogs and pro-drugs of naturally occurring progesterone.
- Natural progesterone is the only therapeutic for TBI in clinical studies that has reproducible results.
- Progesterone analogs unlike natural progesterone are:
- Water soluble and hence can be administered via intramuscular injection or i.v. drip (possibly orally available)
- Easy method of transport and can be reconstituted immediately
- Rapidly reaches Cmax and provide much longer plasma half-lives.
Severe TBI occurs in over 1.1 million people across the US and other major countries. Approximately 250,000 of these cases are in the US. Despite the relatively high incidence of TBI, there is still no clinically effective pharmacological treatment available for TBI. Only a very few candidates for TBI treatment are in the pipeline. Natural progesterone is the only therapeutic agent to date 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 and appears to provide neuroprotection against both the acute and long-term effects of a TBI.
Although successful in clinical settings, progesterone has limitations, particularly during emergency conditions. First, because natural progesterone is lipid-soluble, it is difficult to administer this agent via i.v. in an aqueous formulation, the fastest method of neurosteroid administration. Second, progesterone must be mixed with a carrier in special containers with limited stability. Finally, the plasma half-life of progesterone is very short, which necessitates frequent injections or a continuous i.v. drip in order to maintain effective plasma concentrations. These limitations render natural progesterone far less suitable for first-response situations. The progesterone analogs developed by Emory investigators are water-soluble that could be carried as a powder, reconstituted instantly, and administered immediately via either intramuscular injection or i.v. drip. These analogs reach Cmax very rapidly which reduces the time between injury and the effects of treatment, and they have much longer half-lives than natural progesterone which reduces, or even eliminates, the need for multiple injections during emergency transportation to medical facilities.
Lead compound has been fully characterized and is ready for regulatory required preclinical testing.