EPIC (Expression, Proteomics, Imaging, Clinical) is an intensive observational study of over 500 people with MS who have been carefully studied since 2004. EPIC employs the most advanced imaging, molecular, cellular and bioinformatics techniques to gain greater understanding of MS susceptibility and long-term progression.

Laboratory advancements have allowed us to expand our vision. With the help of our new MS dedicated MRI scanner we are transforming our imaging capabilities and for the first time can visualize specific structures within the spinal cord affected by MS. In the laboratory, new assays and techniques are allowing us to process a greater variety of biological samples allowing us to understand specific MS antibodies found in cerebrospinal fluid. We are also conducting the first large-scale survey of the microbiome in MS. The more information collected, the richer will be our understanding of MS.

Having achieved success in understanding the genetic architecture involved in MS susceptibility and characterizing long-term disability progression in patients treated with disease modifying therapies, EPIC is now focusing on finding the MS trigger. We believe that an as yet unidentified, environmental factor triggers an immunological cascade in genetic susceptible individuals resulting in the clinical manifestations of MS. To find the trigger we need to assemble a large cohort of individuals who are presenting with MS symptoms for the first time. The EPIC study is actively recruiting anyone who recently has been diagnosed with MS or anyone who is suspected of having MS.

Specifically, we are reaching out to persons who have had a recent optic neuritis (inflammation of the optic nerve), transverse or partial myelitis (inflammation of the spinal cord) or encephalitis (inflammation of the brain, brainstem or cerebellum). We are also recruiting individuals without symptoms who have had a recent brain MRI scan that is suggestive of MS.

Below you will find contributions from many of the researchers who dedicate their expertise to the EPIC Study. We hope the information provided illustrates the scope of our study and the way it approaches MS research from every angle in the quest for a cure.

Clinical

Advancing the Clinical Characterization of MS 445x50 clinical
The EPIC Study is a prospective observational cohort of over 500 MS patients who were followed at UCSF for more than 10 years. From studying this cohort we now understand that secondary progressive MS and permanent neurological disability evolves more slowly in the modern treatment era in comparison to the natural history of MS. Nonetheless, we find that over the long-term, neurological disability still occurs in about 50% of treated relapsing MS patients and in most patients with progressive MS underscoring the need for improved therapies, particularly ones that are effective in progressive forms of MS. We also found that routine conventional MRI of the brain does not provide sufficient predictive utility to understand who will be at risk for long-term disability and that other measures including new techniques to image the spinal cord may be more useful for understanding those individuals with MS who are at higher risk for disability.

Watch Dr. Cree's talk about the Clinical Characterization of MS

UCSF MS Center website


Neuroimaging

Imaging MS Evolution Through Space and Time445x50 imaging
The application of quantitative Magnetic Resonance (MR) techniques has been a crucial advancement in the study of disease mechanisms and progression in MS. We strive to monitor changes in all tissue at risk, including spinal cord tissue not previously amenable to analysis. Our imaging methods provide a four-dimensional view of disease evolution, with the application of specific markers indicative of pathology embedded in the structural and functional networks of the central nervous system. The EPIC patient cohort has provided us with the opportunity to advance our methods of analysis and establish a direct connection between white matter lesions and grey matter loss. Central to all future discoveries will be the newly installed 3T MRI magnet in the Sandler Neurosciences Center, which is optimized for the study of MS.

Watch Dr. Roland Henry's talk about Neuroimaging and EPIC

Read more about the new MS dedicated scanner

OCT - Retinal Imaging

The Optic Nerve: A Predictor of Disease Course445x50 oct
The retina, the only part of the central nervous system not covered by bone or skin, is comprised of the same cell types as the brain and spinal cord. Noninvasive, high-resolution retinal imaging in the form of Optical Coherence Tomography (OCT) and detailed visual testing have become integral parts of the EPIC Study. This annual testing has shown us that retinal injury in MS involves more layers of the retina than we thought, and that some of the retinal measures of these deeper layers have the potential to help predict the course of MS in a patient. We have learned that the visual dysfunction experienced by MS patients often occurs in areas not routinely tested, such as color vision and lowlighting conditions. The integration of this information along with the genetic and neuroimaging data, promises to yield exciting new treatments. We are thankful to the EPIC patients who are helping us make these important discoveries.

Watch Dr. Ari Green's talk about Visual Systems and EPIC

Neuroimmunology

Identifying Key Players in Immune-Mediated Damage445x50 immuno
B cells are important in a normally functioning immune system: they initiate targeted attacks against viruses, bacteria, cancers and other unwanted intruders. In MS, however, some B cells appear to play a role in the immune-mediated damage of central nervous system myelin. We are working to discover how culprit B cells develop and how they contribute to MS brain lesion formation. EPIC has been an important resource to identify research participants who are uniquely suited to address these specific research questions. We aim to develop new biomarkers for diagnosis and prognosis of MS and to identify immune system components that can be targeted for new therapies.

Watch Dr. H.-Christian von B├╝dingen's talk about Neuroimmunology and EPIC

Neuroimmunology Lab website

Genetics

Our Genetic Blueprint Shapes the Risk for MS445x50 genechip
Genes play a key role in determining who is at risk for developing MS, how it will progress, and how individuals respond to therapy. Our strategy for gene discovery in MS relies on the meticulous scanning of the entire genome of patients and their relatives to identify the full roster of genetic variants (or alleles) linked to MS. When we began the EPIC project we only knew of a single MS gene. Today, the number of known MS risk genes exceeds 120, with many additional on the verge of being revealed. The next step is to learn how they function. This research is driving a more refined representation of the genetic contributions to disease pathogenesis and risk. Equally important, this information may well reveal novel targets for therapy, prevention and repair.

Watch Dr. Jorge Oksenberg's talk about Genetic Susceptibility

MS Genetics Research Lab

Gene Expression Profiling

In search of biomarkers of disease progression and drug response445x50 gene expression
Although every cell in our body contains the same genes, not all genes are active in all cells. Furthermore, genes turn on and off in response to external stimuli thus producing patterns of activity that can be traced by using state-of-the art technology. We hypothesize that gene expression profiling will be a useful strategy to identify patterns of gene activity in MS patients and that we will be able to correlate those patterns with specific disease stages, or even to predict relapses or response to disease modifying therapies. The identification of the specific genes and transcriptional variants associated with MS will greatly accelerate progress in research and should lead to better strategies to correct or prevent the genetic process that leads to brain inflammation, demyelination, and axonal injury and consequent neurological deficits.

Watch Dr. Baranzini's talk about Gene Expression Profiling

MS Genetics Research Lab

Microbiome

Guts, Bugs, and MS445x50 microbiome
The intestinal tract is inhabited by thousands of beneficial bacterial species (collectively known as gut microbiota). Recent advances allow us to sequence the DNA of these microbiota and have led to exciting discoveries. We hypothesize that the gut microbiota of people with MS is substantially different from that of healthy individuals, and that those changes are an integral component of the pathogenic process that triggers MS. In analyzing the bacterial species of MS subjects and healthy individuals from the EPIC Study, we are confident that this information will help us understand the origins of MS, and devise new therapeutic strategies to treat this disease.

Baranzini Lab Website

Watch Dr. Baranzini's talk about the Microbiome and EPIC

Translational Digital Medicine

UCSF MS BioScreen445x50 bioscreen
It is a challenge for researchers, clinicians and patients to organize, integrate and interpret the vast accumulation of diverse clinical and biologic data. We must bridge numerous datasets including genomic sequencing, gene expression, and MR imaging in order to construct a complete understanding of multiple sclerosis. With the support of data collected from the EPIC cohort, we have developed an exciting new tool, the MS Bioscreen. The Bioscreen will provide an effective and secure digital portal to access and display real-time information for use by patients and health-care providers, and it will promote precision medicine, evidence-based education, and innovative new hypotheses for research.

Watch Dr. Gourraud's talk about the MS Bioscreen

MS Bioscreen website

For past newsletters from the EPIC project, please click on one of the following links.
2005 Newsletter | 2010 Newsletter | 2013 EPIC Update