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.

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. 

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

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.

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.

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.

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.

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.