Embargoed by Proceedings of the National Academy of Sciences until Monday, September 15, 5:00 p.m.
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Synthetic Steroid Dramatically Reduces Stroke Damage; Heralds New Class of Drugs
A research team at Boston University School of Medicine has discovered that a synthetic compound significantly limits brain damage when administered after a stroke. Their finding, published September 16 in the Proceedings of the National Academy of Sciences, could lead to the development of drugs to treat stroke and traumatic brain or spinal cord injury. These new drugs could also slow the progression of ParkinsonÃs disease and ALS, more commonly known as ìLou GehrigÃs disease.î Half a million people are afflicted by stroke (the third leading cause of death in the United States) each year, and nearly one million suffer from ParkinsonÃs disease and ALS.
According to David H. Farb, PhD, professor and chair of the department of Pharmacology, the compound, derived from a naturally occurring steroid and known as pregnanolone hemisuccinate, can be easily and inexpensively produced. ìThis compound has remarkable neuroprotective properties,î says Farb. ìIt represents the first of a new class of potentially useful therapeutic agents to treat stroke and several other neurodegenerative diseases.î
According to Farb, neurons die when exposed to excess amounts of a substance called glutamate. Glutamate is released in the brain and spinal cord when a special molecule known as an NMDA-receptor is over-activated. ìWhen a person has a stroke, oxygen canÃt get to neurons and they die. But in dying those neurons release large amounts of glutamate, which activates the NMDA-receptors of neighboring neurons, which in turn produce more glutamate and kill more neurons. ItÃs a vicious cycle, and the secondary damage can often be worse than the initial event,î he says. However, pregnanolone hemisuccinate ìdeactivatesî the NMDA-receptor, halting glutamate release. Thus, the secondary damage is confined, and far fewer neurons die. The study utilized middle-cerebral artery occlusion (blockage) in rats, the common protocol for animal studies on stroke.
Farb believes that pregnanolone hemisuccinate will fundamentally change the manner of treating stroke. ìRight now, we donÃt have a good treatment for stroke. Currently, the only accepted treatment for stroke is the drug TPA, which is extremely expensive, only somewhat effective and canÃt be used in all types of stroke,î he says. ìPregnanolone hemisuccinate or related compounds promise to be far less costly, more effective and may be beneficial for all strokes.î
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