The Center for Neurovirology and Neurodegenerative Disorders (CNND)
at the University of Nebraska Medical Center 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 brains immune system
can lead to damage of nerve cells in HIV-dementia and Alzheimers 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 grants 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.
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), Alzheimers disease and Parkinsons
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.
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 brains 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.
By 2010, it is estimated that nearly 60,000 Nebraskans will develop
Alzheimers disease, Dr. Gendelman said.
From a scientific prospective, the pivotal cells involved in neurodegenerative
disease are the microglia — the brains 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 Alzheimers disease, HAD and other degenerative brain disorders.
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. Gendelmans leadership, UNMC
has become a national powerhouse with regard to the study of immune function
in neurodegenerative disorders such as Alzheimers 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.
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.
Although the greatest measure of the CNNDs 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 Gehrigs
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.