Epilepsy Drug May Delay Alzheimer’s Progression
URMC Leads 30-Center Trial Focusing on "Tangles"
Monday, November 10, 2003
Until we have a cure for Alzheimer’s, we are continually searching for ways to provide patients with prolonged autonomy so they can live their life to the fullest for as long as possible.
A medication that has been around for 20 years and successfully used to treat epilepsy, migraines and bipolar disorder may provide new hope for the more than four million Americans suffering with Alzheimer’s disease. The University of Rochester Medical Center is launching a national study involving 30 institutions (see below for complete list) to determine if the medication valproate preserves functioning and delays the expected decline associated with Alzheimer’s disease.
The $10 million study will target 300 patients with mild to moderate Alzheimer’s who are living at home and have not yet shown signs of agitation. One of the personality changes that Alzheimer’s patients experience, symptoms of agitation include easy to anger, low frustration level, and at its worst, physical aggression. The latter is one of the primary symptoms that prompt families to place loved ones in a skilled nursing facility.
Scientists will study whether patients who take valproate experience less agitation, as well as whether valproate will slow down the deterioration of memory and daily functioning that occurs as the disease progresses. And, according to Pierre Tariot, professor of psychiatry, and project director of the “Valproate in Dementia” or VALID study, there’s good reason to conduct this study.
“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,” Tariot said. “We are eager to learn whether these neuroprotective effects that valproate exhibited in the laboratory will also occur in Alzheimer’s patients.”
The VALID study is the first of its kind to study an agent that may have the potential to block “tangles,” one of the hallmarks of Alzheimer’s disease linked with memory loss and other symptoms of dementia. Tangles are abnormal brain tissue structures formed by abnormal processing of a protein called tau. Normally, tau is crucial for intracellular functioning and structure, but in Alzheimer’s patients, a stringy cluster of tau and phosphate molecules form, leading to dysfunction that impairs the cell’s ability to communicate with neighboring cells. This eventually leads to cell death, contributing to the confusion, disorientation and forgetfulness associated with Alzheimer’s.
Tariot and his colleagues in Rochester have previously studied valproate in Alzheimer’s patients already showing signs of agitation. His study, and two others, have shown valproate to provide a beneficial effect for agitation in some patients.
“Until we have a cure for Alzheimer’s, we are continually searching for ways to provide patients with prolonged autonomy so they can live their life to the fullest for as long as possible,” Tariot said.
The VALID study will follow the 300 patients over two years. While in the study, patients may continue standard treatment with other medications. In addition to examining valproate’s possible effect on slowing progression of symptoms of the illness, researchers will also conduct two ancillary studies. One concerns a blood test that will investigate how Alzheimer’s affects the manufacture of critical cell products, messenger RNA and protein. The other will use repeated MRI scans in a subset of 200 people to determine if valproate slows or alters the expected loss of whole brain volume in Alzheimer’s.
VALID is funded primarily with a grant by the National Institutes of Health. In addition, Abbott Laboratories is donating valproate and the placebo medication, as well as the funds to finance the two ancillary studies.
For more information on the VALID studies, please call 585/760-6585.
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Participating VALID Sites
- Case Western Reserve University, Cleveland, OH
- Columbia University, New York, NY
- Emory University, Atlanta, GA
- Georgetown University Medical Center, Washington, DC
- Indiana University, Indianapolis, IN
- Mayo Clinic, Jacksonville, FL
- Medical University of South Carolina, North Charleston, SC
- Brown University, Pawtucket, RI
- VA Healthcare System Long Beach, Long Beach, CA
- Psychiatric Consultants, Nashville, TN
- North East Ohio Health Services, Beachwood, OH
- Northwestern University, Chicago, IL
- Palm Beach Neurological, West Palm Beach, FL
- Radiant Research San Diego, San Diego, CA
- Southwestern Vermont Medical Center, Bennington, VT
- St. Louis University, St. Louis, MO
- Stanford/VA Aging Clinical Research Center, Palo Alto, CA
- Syracuse VA Medical Center, Syracuse, NY
- University of California, Irvine, CA
- University of California, Los Angeles, CA
- University of Nevada, School of Medicine, Las Vegas, NV
- University of Michigan, Ann Arbor, MI
- University of Pennsylvania, Philadelphia, PA
- University of Rochester Medical Center, Rochester, NY
- University of South Florida, Tampa, FL
- University of Southern California, Los Angeles, CA
- University of Texas Southwestern Medical Center, Dallas, TX
- University of Virginia, Charlottesville, VA
- Wien Center, Miami Beach, FL
- Yale University School of Medicine, New Haven, CT