Collaborative MS Research Center Award
||Jorge R. Oksenberg, PhD
University of California at San Francisco
San Francisco, CA
Parvin Mousavi, PhD
Queen's University, Ontario, Canada
Daniel Pelletier, MD
David Mohr, PhD
Sergio Baranzini, PhD
University of California at San Francisco, San Francisco, CA
To combine novel technological and analytical approaches for the discovery of molecules that may be used as "markers" to predict progression of disease in multiple sclerosis.
MS is a highly unpredictable disease. Not only are the symptoms or even timing of attacks unpredictable, there are no laboratory or clinical tests that can predict the future course of this life-long disease.
Dr. Jorge R. Oksenberg—who has been involved in MS genetics for more than a decade—has gathered a team that will integrate state-of-the-art magnetic resonance imaging (MRI) technology, molecular biology techniques, and clinical information to develop a unique approach to predicting MS progression. The approach is based on the hypothesis that MRI images reflect specific molecular and cellular events that occur as the blood-brain barrier (BBB, the lining of cells that protects the brain) is breached in MS. Changes in the activity of these molecules and cells may precede MRI-detected abnormalities, and may be used as "markers" to predict them.
To test this ideas, Dr. Oksenberg's team is collecting and analyzing MRI data and blood samples taken every two months from a group of 112 well-studied persons with MS. These participants are being recruited by psychiatrist Dr. David Mohr and MRI specialist Dr. Daniel Pelletier as part of an NIH-funded study seeking to discover MRI changes associated with stress. Dr. Mohr is collecting clinical information on the rate of relapses, progression of disability, and neuropsychological impairment. Dr. Pelletier is acquiring and analyzing the MRI data, extracting information on lesion volume, tissue loss, changes in brain tissue volume, and other characteristics.
Using blood samples taken at the beginning of the study, genetics specialist Dr. Sergio Baranzini is using microarray technology - which allows for the analysis of thousands of genes at once - to evaluate the activity of more than 21,000 genes in the blood of the participants. The group will look at the activity of these genes in blood samples collected by Dr. Mohr on the day of each MRI scan.
Dr. Oksenberg will screen the blood sample using mass spectrometry, which can identify thousands of proteins at once. He is seeking to identify the molecules associated with increased gene activity. This strategy - known as "proteomics" - aims at identifying the molecular biomarkers much needed in MS for monitoring disease progression and responses to therapy.
The changes in gene expression and proteomics are being correlated with clinical endpoints of interest, such as type of therapy, EDSS scores (which measure disability), and number of relapses. The information will be integrated in a computer model with the expertise of Dr. Parvin Mousavi, a talented young computer scientist.
Dr. Oksenberg and colleagues are attempting to develop an updated model of the molecular dynamics of how myelin and other nerve tissues are damaged, and how MS develops and progresses. He has assembled a truly multidisciplinary team with outstanding expertise in MS clinical care, biomedical imaging, molecular biology, and advanced statistics and data mining, to accomplish this goal.