Stroke — BMS-204352
Stroke is caused by the blockage or rupture of a blood vessel in the brain, and is a major cause of death and disability. The interruption of the blood supply leads to damage in the brain tissue, impairing the function of the affected part of the brain. This can mean loss of movement, sensation or even death. The two most important factors that increase the likelihood of stroke occurring are hypertension and atherosclerosis.
Strokes are classified into several groups. Cerebral thrombosis, where a clot builds up in the wall of an artery in the brain, accounts for nearly half of all strokes. Another third are caused by cerebral embolism, where a blockage, usually a clot, is carried into one of the brain's arteries. The remainder are a result haemorrhage, where a blood vessel ruptures and bleeds into the brain.
Two main approaches are used for treatment: increasing blood flow, and neuroprotection to limit the effects of ischaemia on the brain. Drug agents for the latter purpose concentrate on suppressing the mechanisms in the brain that increase the susceptibility of the central nervous systems to the effects of ischaemia. Drugs categories with this effect include free radical scavengers, GABA agonists, calcium and sodium ion channel blockers and potassium channel openers.
A new drug in development at Bristol Myers Squibb that operates by the last of these mechanisms is the voltage-dependent K+ channel opener BMS-204352.1,2 It acts on the so-called maxi-K channel, which are large conductance Ca2+ activated K+ channels, and they limit the entry of calcium ions into cells. There are many such channels in the brain, and BMS-204352 has been shown to open maxi-K channels in animal models.
Clinical trials have shown the compound to be safe and well tolerated. Patients were given i.v. doses at varying levels and frequencies of the drug. No clinically significant adverse effects were seen in stroke patients. Both healthy and stroke patients showed a high clearance, extensive distribution and a half life of 16–20hr.3,4
The compound is now in Phase III trials to evaluated its efficacy and safety as a therapy for the treatment of ischaemic stroke.