CNND receives $6 million grant for neurodegeneration studies

by Tom O'Connor, UNMC public affairs | August 05, 2003

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Members of the CNND.
The Center for Neurovirology and Neurodegenerative Disorders (CNND) at UNMC has received a $6 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health to study how the brain's immune system can lead to damage of nerve cells in HIV-dementia and Alzheimer's disease. The research also will seek to determine how arms of the immune system can be harnessed to reverse different forms of dementia.

The grant, which provides funding over five years, is a program project grant. Program project grants are highly competitive grants and given to large complex research projects requiring multidisciplinary support spanning distinctly different scientific areas. Because of their complexity, the grants often involve collaboration between several institutions. This, however, is not the case for this grant. Only one institution -- UNMC -- is involved and the support goes to CNND scientists.

"We are proud that the CNND has reached a milestone in its development and that it can compete on its own merit for these sums of money," said Howard Gendelman, M.D., director of the CNND and the grant's principal investigator. "By any measure we have become a bona fide neurosciences center. A solid infrastructure that encompasses a wide variety of scientific disciplines is now in place including immunology, virology, protein chemistry, molecular biology, neuropharmacology, cognitive neuroscience and radiology."

CNND's groundbreaking discoveries

The CNND, which was established in 1997, now includes more than 70 scientists and support staff. This diverse group includes scientists from nine different countries.

Dr. Gendelman said the research will center around previous groundbreaking discoveries made by CNND investigators that inflammatory activities are implicated in a number of neurodegenerative disorders including, but not limited to, HIV-1-associated dementia (HAD), Alzheimer's disease and Parkinson's disease. The CNND scientists believe that the interplay between the immune system and the brain may be harnessed to counter the death of brain cells due to viral infection or during neurodegenerative processes. It is this balance between immune activities that may underlie the process of dementia and a number of motor abnormalities associated with the aging process.

Understanding the brain's immune system

The CNND will seek to determine if altering the composition of immune activities can positively affect disease and provide new and novel directions to prevent or retard diseases and improve diagnostic capabilities. Currently there are limited therapeutics available to positively affect the disease course in most neurodegenerative diseases.

"Our primary focus will be to study the specific immunologic bases of HAD and the linkages between HAD and other neurodegenerative disorders," Dr. Gendelman said. "Understanding how the brain's immune system becomes compromised is critical in developing vaccines or other therapeutic modalities in the search for better treatments for all people afflicted with such horrific neurodegenerative conditions. We believe strongly that neurodegeneration can be reversed, at least in part, through drug or immune manipulations."

Neurodegenerative diseases

By 2010, it is estimated that nearly 60,000 Nebraskans will develop Alzheimer's disease, Dr. Gendelman said.

From a scientific prospective, the pivotal cells involved in neurodegenerative disease are the microglia -- the brain's scavenger -- and a pivotal immune regulatory cell. It is thought that the microglia and other brain immune cells cause degenerative events by secreting toxic molecules. Such events link all research efforts for this grant and provide a bridge between studies of Alzheimer's disease, HAD and other degenerative brain disorders.

Dr. Lipton: UNMC is a national powerhouse

"The diverse expertise of CNND investigators allows us to maintain a unified focus on how the immunobiology of the brain can both affect neurodegeneration and neuroprotection," Dr. Gendelman said. "This is what makes the science so strong and allows us to compete at the national level."

A member of the CNND Advisory Board and a noted neuroscientist/neurologist, Stuart A. Lipton, M.D., Ph.D., scientific director of the Burnham Institute and professor at The Salk and Scripps Research Institutes and the University of California -- San Diego said, "Under Dr. Gendelman's leadership, UNMC has become a national powerhouse with regard to the study of immune function in neurodegenerative disorders such as Alzheimer's disease and HIV-associated dementia. I fully expect this new grant to lead to further inroads into the understanding of these disorders and, eventually, to new therapeutic avenues."

Scientists have vast expertise

"The CNND scientists have significant expertise in neurotoxicology, cellular immunology, neuropathology, neurophysiology, neuropharmacology and molecular biology," Dr. Gendelman said. "We have established a unique niche in neuroscience research through our use of state-of-the-art technologies in magnetic resonance imaging/spectroscopy, electrophysiology and proteomics."

Most senior CNND scientists are involved in this research study and include Yuri Persidsky, M.D., Ph.D., Tsuneya Ikezu, M.D., Ph.D., Jialin Zheng, M.D., Huangui Xiong, M.D., Ph.D., Anuja Ghorpade, Ph.D., R. Lee Mosley, Ph.D., Michael Boska, Ph.D., and Larisa Poluektova, Ph.D.

Strong grant history

Although the greatest measure of the CNND's research has centered on HIV, this marks the third significant federal grant the CNND has received for studying brain disease extending beyond HIV. Other funding includes a significant federal grant to Dr. Persidsky to study alcohol affects on the nervous system; a five-year grant in collaboration with Columbia University to study vaccine approaches for amyotrophic lateral sclerosis (Lou Gehrig's disease) based, in part, on the work of Eric Benner, a CNND graduate student; and pharmaceutical grants from Pfizer and Baxter Inc. in the areas of nanotechnology and brain imaging to support the work of Dr. Mosley and Jenae Limoges, M.D.

Earlier this year, Dr. Gendelman received the UNMC Career Research Award for Internal Medicine as well as a merit award from the NIH for his work in mentoring young minority scientists through a collaborative program grant with the University of Puerto Rico.