Systems Biology Provides First Global Analysis of Prion Disease in a Mouse Model

Approach Could Point to Mad Cow Diagnostic Blood Markers, New Treatment Targets
in Humans and Application of Systems Approaches to Other Diseases
SEATTLE--(Business Wire)--
Researchers at the Institute for Systems Biology (ISB) in Seattle and the
McLaughlin Research Institute in Great Falls, Montana, published today in
Molecular Systems Biology a ground-breaking study which modeled the progression
of degenerative brain diseases, one of which is "mad cow disease," that are
caused by misfolded proteins called "prions". The paper can be accessed at
http://www.nature.com/msb/index.html.

The study is perhaps the first comprehensive use of a "systems approach" leading
to fundamental new insights into degenerative brain disease, as well as paving
the way for new approaches for early diagnosis. The systems approach employs
comprehensive (global) studies of informational molecules in the brain
throughout the course of the disease and permits the construction of predictive
models regarding disease mechanisms.

A review of the study in the same edition of Molecular Systems Biology by
Gilbert S. Omenn, M.D., Ph.D., professor of Internal Medicine, Human Genetics,
and Public Health Director at the University of Michigan Center for
Computational Medicine and Biology, lauded the study as likely to become a
landmark paper in systems biology for its methods and findings.

"This study is an example of how predictive network models of disease can be
used to understand disease in an entirely new way, not as collections of
symptoms, but rather as systems of interacting biological molecules that are not
working properly," said Leroy Hood, M.D., Ph.D., president and co-founder of
ISB. "Understanding these biological systems will allow us to diagnose, treat
and ultimately prevent neural degenerative diseases. This systems approach will
be a powerful new tool for studying virtually any type of disease."

ISB and McLaughlin researchers analyzed the complete populations of brain
messenger RNAs in infected and control animals at 10 different time points
during the disease progression. From these data, the research team was able to
identify about 300 changing messenger RNAs that encoded the core prion disease
response.

The identification of these RNAs enabled researchers to discover and describe
four biological networks that explain virtually every known aspect of prion
disease. The research team was also able to determine that about 100 of these
prion-core RNAs encoded aspects of this disease that were previously unknown.
Three of the four biological networks are also apparently involved in human
neurodegenerative diseases such as Alzheimer`s and Huntington`s diseases. These
studies also suggested possible new approaches to therapy for prion disease and
other neurodegenerative disease.

Based upon the analysis of the disease-perturbed networks, researchers were also
able to identify several protein blood biomarkers that indicate the presence of
prion disease prior to the development of symptoms. Early detection can be
important both for the management and more effective treatment of many diseases.

George Carlson, Ph.D., Director of the McLaughlin Research Institute in Great
Falls, Montana, pointed out the importance of modeling disease in mice. "Mice
offer the tremendous advantage of being able to track disease-associated changes
in the target organ, in this case the brain, well before clinical illness
appears," he said.

"We then look for changes in the blood that track with changes in the brain in
mice that could be used as diagnostic signatures in specific disease models,
such as frontotemporal dementia or Alzheimer`s disease," said Carlson. "Results
from mice will point the way for identification of blood diagnostic tests in
humans."

These studies were based on approximately 30 million measurements, which
required researchers to develop a series of powerful new software programs for
analyzing, integrating and finally modeling these enormous amounts of data.

About the McLaughlin Research Institute

The McLaughlin Research Institute is an independent non-profit research
organization in Great Falls, Montana near the Rocky Mountain Front. Research at
the institute focuses on understanding the genetic control of normal development
and disease susceptibility using the mouse as a model system. The Institute
began in 1954 as the Laboratory for Experimental Medicine founded by Dr. Ernst
Eichwald, a pioneer in transplantation genetics. Current research by its four
research teams and forty-plus staff members emphasizes application of mouse
genetics to understanding neurological disorders including Alzheimer`s disease,
prion disorders, Parkinson`s disease, epilepsy, peripheral neuropathy, and
sensory disorders. For more information on MRI visit: www.montana.edu/wwwmri

About the Institute for Systems Biology

The Institute for Systems Biology (ISB) is an internationally renowned,
non-profit research institute headquartered in Seattle and dedicated to the
study and application of systems biology. Founded by Leroy Hood, Alan Aderem and
Ruedi Aebersold, ISB seeks to unravel the mysteries of human biology and
identify strategies for predicting and preventing diseases such as cancer,
diabetes and AIDS. ISB´s systems approach integrates biology, computation and
technological development, enabling scientists to analyze all elements in a
biological system rather than one gene or protein at a time. Founded in 2000,
the Institute has grown to 14 faculty and more than 250 staff members; an annual
budget of more than $35 million; and an extensive network of academic and
industrial partners. For more information about ISB, visit
www.systemsbiology.org.

Institute for Systems Biology
Todd Langton, 206-732-1333
tlangton@systemsbiology.org

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