February 2, 2001

Montine named Thorne professor

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Montine named Thorne professor

Dr. Thomas J. Montine, associate professor of Pathology and Pharmacology now holds the Margaret and George Thorne Professorship in Pathology, one of several professorships at Vanderbilt University Medical Center designed to recruit and retain outstanding faculty.

Montine, who has been on the Vanderbilt faculty since 1996, is devoting much of his time trying to find out what damage occurs, and how, in the brains of patients with neurodegenerative diseases. He is focusing on new pharmacological targets in age-related neurodegenerative disorders such as Alzheimer's disease and Parkinson's Disease.

Much of the current research in neurodegenerative diseases focuses on trying to understand what triggers the death of neurons, and how to best measure the disease progression and response to therapy.

"We have to understand the mechanisms that underlie these diseases, the engines that make them go. Our focus is based on free radical damage to the brain," he said. "The goal is to define the important pathological pathways, the abnormal neurochemistry that's going on, and through that clarification, identify new therapeutic agents."

From this knowledge of mechanisms of disease, Montine's laboratory also hopes to identify biomarkers to be used in the evaluation of patients with neurodegenerative diseases.

"Right now we don't have very facile ways to diagnose Alzheimer's disease or Parkinson's Disease. Nor are there indices of how severe Alzheimer's or Parkinson's Disease is or how quickly it's moving forward," Montine said. Currently, Alzheimer's disease can only be confirmed by examining the brain after death.

Bolstered by grants from the Alzheimer's Association and the National Institutes of Health, Montine's laboratory is working with Drs. Jason D. Morrow, F. Tremaine Billings Professor of Medicine and L. Jackson Roberts II, professor of Pharmacology and Medicine, on basic biochemistry and animal model systems of free radical damage to the brain.

Montine, Morrow and Roberts have studied isoprostanes and a newly described class of molecules, neuroprostanes, in Alzheimer's Disease. In collaboration with neurologists at the University of Kentucky, Massachusetts General Hospital, and Oregon Health Science University, they have shown that the levels of these molecules in cerebrospinal fluid are significantly increased early in the course of dementia and correlate with disease severity. These findings support a role for free radical damage to the brain early in Alzheimer’s Disease and have important implications for therapy.

"I think a major contribution of our work will be to determine the relative effectiveness of experimental therapeutics in limiting free radical damage to the brain," Montine said. "They may also make a meaningful contribution to diagnosis."

Recently, Montine and his collaborators have shown that cerebrospinal fluid isoprostanes combined with other established laboratory tests increase the diagnostic accuracy for Alzheimer's disease.

Montine is taking a similar approach with the second most common neurodegenerative disease, Parkinson's Disease. Here, Montine's laboratory works closely with Dr. Ariel Y. Deutch, professor of Psychiatry and Pharmacology and director of the National Parkinson's Foundation Center of Excellence at VUMC.

"Although less developed than our work in Alzheimer's disease, we're also investigating the mechanisms that drive the progression of Parkinson's Disease and developing cerebrospinal fluid biomarkers to assess the severity of Parkinson’s Disease," Montine said. "The biochemistry is different than Alzheimer's disease but the logic is the same."