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Gamma Secretase Inhibitors: Meant for Alzheimer's but Also Helpful for Brain Trauma?

Posted Mar 17 2009 4:22am
Georgetown University scientists have studied the use of gamma secretase inhibitors (GSIs) to prevent permanent brain injury after head trauma, in mice. GSIs prevent the formation of amyloid buildup in the brain, in order to prevent or mitigate the amyloid plaques of Alzheimer's disease.

Interestingly, amyloid also accumulates in the brains of persons with brain injuries -- even very young victims of head injury.
Researchers at Georgetown University Medical Center will publish their findings in an advance online publication of Nature Medicine.

They say the results suggest that this class of drugs could potentially do something no other drug has been able to do — prevent the long-term and continuing damage that often follows a serious injury to the brain.

That is because the agents, known as gamma secretase inhibitors, are designed to prevent buildup of amyloid, a toxic peptide found in the brain. This peptide clogs the brains of Alzheimer’s patients but it is also found in people who have died from traumatic brain injury, says the study’s lead author, neuroscientist Mark Burns, Ph.D, an assistant professor at GUMC.

“No one knows why it occurs, but abnormal amounts of amyloid plaque have been found during an autopsy in about a third of brain injury victims, some of whom were children who would ordinarily never have had these deposits,” says Burns. _ PsychCentral
Amyloid deposits can begin building as soon as 1 day after injury -- demonstrating how dynamic a contribution amyloid may make to long term brain damage.

It is hoped that rapid diminution of amyloid deposits will lead to brain recovery in both Alzheimer's patients and in victims of traumatic brain injury. For mice, the treatment was successful in blocking permanent brain damage.

GSIs are currently investigational drugs. If they can demonstrate efficacy for both Alzheimer's and traumatic brain injury, clinicians can hope for a dual approval when the drugs are released.
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