Tisch MS Scientists Presented at AAN 2013

Four posters by Tisch MS scientists were accepted by the American Academy of Neurology for presentation at the Academy's annual conference, held March 16-23 in San Diego, CA. The posters presented at AAN 2013 are:

L.H. Bell, V.K. Harris, and S.A. Sadiq. "Identification of CSF biomarkers of cognitive impairment and cerebellar dysfunction in multiple sclerosis."

Summary: Cerebellar and cognitive deficits are common symptoms in MS, contributing to significant disability in a subset of patients. This study sought to identify and validate biomarkers of cerebellar/cognitive deficits in the cerebrospinal fluid (CSF) of MS patients. We found that specific proteins in the amyloid processing pathway (APLP2, sAPPbeta, and Abeta40) were significantly reduced in the CSF from MS patients exhibiting severe cognitive impairment and cerebellar dysfunction. Pending further validation, these biomarkers allow further insight into pathophysiological mechanisms underlying this system complex.

B.H. Yoon, A. Mueller, E. Franzova, and S. Sadiq. "A Proof of principle study: Diagnosing MS by analyzing the CSF cell transcriptome."

Summary: Cells in the cerebrospinal fluid (CSF) likely have interacted with or have derived from inflammatory CNS lesions and thus are of interest because they are representative of disease activity. To better understand mechanisms in MS and to identify potential disease biomarkers, this study analyzed the gene expression profile of CSF cells using microarray. We found a B-cell gene signature that distinguishes MS patients´ CSF cell transcriptome from control patients´ transcriptome. This proof-of-principle study demonstrates that the CSF cell transcriptome is a usefull tool for MS diagnosis.

H.J. Ray, D. Lee, F. Mir, and S. Sadiq. "Correlation between oxidative stress and chemokines in the cerebrospinal fluid of multiple sclerosis patients."

Summary: The current study investigates the relationship between oxidative stress and chemokines in multiple sclerosis (MS). Chemokines are known to modulate generation of reactive oxygen species (ROS) at the site of inflammation. This association between ROS and inflammation, was viewed as a one-way process, i.e. immune cells activated by chemokines produced ROS. However, excessive ROS production disturbs redox status, damages macromolecules, and can modulate the expression of a variety of immune and inflammatory molecules, exacerbating inflammation and affecting tissue damage. We found that the levels of the chemokines – IL-8/CXCL8, MCP-1/CCL2 and IP-10/CXCL10 are increased in the cerebrospinal fluid (CSF) of MS patients with increased oxidative stress. We are currently investigating this interplay between oxidative stress and immune activity at a cellular level.

J.W. Stark, D. Koffler, and S.A. Sadiq. "Persistence of Cerebrospinal Fluid Oligoclonal Bands after Natalizumab Treatment of Multiple Sclerosis Patients."

Summary: In 2012, a paper in the journal, Multiple Sclerosis, by Glehn et al reported the disappearance of oligoclonal bands in the spinal fluid of four out of six MS patients treated with Natalizumab (Tysabri). Oligoclonal bands (or OCBs) are immunoglobulins found in the spinal fluid of MS patients approximately 80-90% of the time. Based on what we know about OCBs and Natalizumab, I was skeptical of these results and attempted to replicate the study. What I found was that nine out of eleven patients still had OCB’s in their spinal fluid after Natalizumab and one patient, who did not have bands before Natalizumab, then tested positive afterwards. I believe the differing results are because our study had four times more patients than the original study.