Analyzing EBV Genomes and Epigenomes and EBV-Dependent B Cell Proteomes to Identify Fundamental Viral Triggers of MS
Abstract
Understanding how Epstein Barr Virus (EBV) Causes Multiple Sclerosis: The objective of this proposal is to learn about the genetics of EBV and how it contributes to the development of multiple sclerosis (MS). Approximately one million Americans suffer from MS. It is the most common cause of disability in young adults. MS is an autoimmune disease in which the patient s own immune cells attack components of the central nervous system (CNS, brain and spinal cord). Common symptoms include loss of vision, fatigue, numbness and tingling, muscle spasms and stiffness, bladder problems, and weakness. Prior research has shown that 100% of MS patients have been infected with EBV before their initial symptoms. EBV is therefore considered to be a pre-requisite to developing MS. However, the large majority of the general population is also infected with EBV, and it is unclear why some individuals develop MS and others do not. The overarching objective of this proposal is to identify fundamental molecular mechanisms by which EBV alters the patient s immune system to promote development of MS. Over the last decade our laboratories have developed several unique technologies to study the role of EBV in MS, which include methods to characterize the immune response to viral components and ways to sequence the viral DNA itself. This award will enable us to use our molecular technologies to investigate how EBV contributes to the development of MS. In particular, we will answer two important questions: Do cells from MS patients that become infected with EBV react differently to the virus than the same cells in healthy individuals? And are there distinct sub-strains of EBV that cause MS? This proposal will address the Focus Area Factors Contributing to or Associated with MS Etiology, Prodrome, Onset, and Disease Course. By addressing the etiology of MS, our research will address fundamental questions in MS research: What is the cause of the disease? What are the main molecular mechanisms that explain the association between the major risk factor EBV and the development of MS? MS is a complex and very heterogeneous disease that requires individualized therapeutic strategies. As our research tackles a fundamental question of MS, we anticipate that our results will be relevant to all MS patients. In addition, it could be possible that we identify several distinct kinds of immune cell responses and certain EBV sub-strains, which distinguish some groups of patients from others, and which could be further developed for use as biomarkers to guide therapeutic decisions. Understanding the molecular mechanisms that cause MS will also enable us to design novel fundamental therapies for the treatment of MS. These include antiviral therapies, therapies that influence the immune response to EBV, or vaccines against EBV. While currently antiviral therapeutics against EBV show limited efficacy, there are several antiviral treatments for other related herpesviruses. Their development have equipped the scientific community with an extensive amount of experience in this field that can be utilized to develop improved therapies against EBV. Several development campaigns are ongoing at the moment and their timelines will be relatively short. Further, multiple vaccine trials against EBV are currently ongoing, including two mRNA vaccine trials by Moderna. In addition to antiviral therapeutics, there are multiple therapeutic compounds that interfere with activating pathways in immune cells. Upon discovery of the relevant pathways, we can repurpose these existing therapeutic compounds to treat EBV and its effect on immune cells in MS patients. Thus, success of the proposed studies in demonstrating how EBV promotes MS could be rapidly translated into novel therapies for MS patients. These therapies would likely be effective and more specific than current therapies, which for the most part have promiscuously large effects on the immune
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310595
Entities
People
- Tobias Lanz
Organizations
- Stanford University
- United States Army