Psychiatric News March 5, 2004
Volume 39 Number 5
© 2004 American Psychiatric Association
p. 52
Epilepsy Drug May Slow Progression Of Alzheimer’s
Mark Moran
Valproate may increase the expression of a protein that slows the cell death that neurons undergo in Alzheimer’s. It may also inhibit production of an enzyme involved in production of neurofibrillary tangles.
A multisite, placebo-controlled trial funded by the National Institute on Aging will study the utility of valproate in prophylactically delaying the emergence of agitation or psychosis in outpatients with Alzheimer’s disease.
A target dose of valproate at approximately 10-12 mg/kg per day will be tested in outpatients with probable Alzheimer’s. They will be treated for 24 months, followed by a two-month washout.
The drug has long been used to treat epilepsy in children and adults and now is used for a number of indications, such as treating mania in bipolar I disorder.
The study is sponsored by the Alzheimer’s Disease Cooperative Study (ADCS), through an agreement between the National Institute on Aging and the University of California at San Diego to develop trials for agents designed to ameliorate behavioral symptoms, improve cognition, slow the rate of decline, or delay the appearance of Alzheimer’s.
The lead researcher in the study is Pierre Teriot, M.D., of the departments of psychiatry and neurology at the University of Rochester Medical Center.
Approximately 300 participants from 25 to 35 centers in the United States will be enrolled.
Alexander Auchus, M.D., clinical director of the University Hospital Memory and Aging Center at Case Western Reserve University School of Medicine and University Hospitals of Cleveland—a participating research site—told Psychiatric News that the study represents a novel clinical-trial strategy to assess both prospective "prophylactic" therapy for psychopathology in Alzheimer’s and an approach that may slow the disease once it has already begun.
Auchus explained that valproate may work in several ways to protect against Alzheimer’s or slow its progression. One way is by increasing the expression of a protein, bcl2, which is known to slow "apoptopsis," the self-induced cell death that neurons undergo in Alzheimer’s.
Another way is by inhibiting production of the enzyme Gsk3b, which is believed to be involved in the production of neurofibrillary tangles, a hallmark of Alzheimer’s.
"When we began to look at valproate in the laboratory, we were amazed to see that this simple drug blocked several key molecular events that we know are involved in the progression of Alzheimer’s," Auchus said. "We are eager to learn whether these neuro effects that valproate exhibited in the laboratory will also occur in Alzheimer’s patients." 
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