Regional Atrophy as a Biological Correlate of MS Progression
Abstract
Background: Despite a wealth of treatments for relapsing remitting multiple sclerosis (MS), developing effective treatments for patients with progressive forms of MS remains a significant unmet need. Current FDA-approved treatments typically target inflammation, which is much lower in progressive MS. As treatments are developed that potentially protect the brain from detrimental changes in progressive MS, it becomes vital to have better ways of evaluating their benefit. MRI is potentially a method to evaluate these treatments, in a shorter period of time, and with fewer patients participating in order to determine the effectiveness of a therapy in reducing disability. Loss of brain tissue is observed in MS and is considered related to worsening of clinical disability and increased difficulties with memory and other cognitive functions. However, there are advantages to looking at tissue loss in brain regions most affected by MS rather than measuring tissue loss in the entire brain. This application focuses on the thalamus, a small region deep in the brain that functions as a relay center for carrying impulses to and from brain cells and the rest of the body. The corpus callosum, a structure that carries many of the connections between the two sides of the brain, is another region of interest. A third region of interest is the cerebellum, the part of the brain that controls balance, which also plays a role in cognitive functions. This proposal addresses the FY17 MSRP Focus Area Biological Correlates of Disease Activity and Progression in MS by evaluating tissue loss in these brain regions in an effort to evaluate treatments that can protect MS patients from developing disability. Hypothesis or Objective: Our overall hypothesis is that changes in regional measures of tissue loss relate to progression of disability and worsening cognitive ability in MS. We hypothesize that studying brain regions more affected by MS will allow for clinical trials with shorter durations and fewer patients. We will use clinical trial data evaluating Ibudilast, a treatment thought to protect the brain from tissue loss in progressive MS, to evaluate these MRI measures. We aim to improve our ability to determine the boundaries of these structures for measurement using software tools that require little to no editing by hand. Applicability of Research: This research has potential to help all patients with MS. We will improve our ability to measure the volume of the thalamus, corpus callosum, and the cerebellum in an automated way and with improved accuracy. This also helps evaluate new treatments for all patients with MS of any subtype and helps our ability to monitor how patients are responding to their disease-modifying therapies. This proposal uses data already acquired from the SPRINT-MS clinical trial. However, the measures we will study were not included in the original aims of the clinical trial. Thus, pursuing this research project poses minimal additional risks to patients. This project will improve our understanding of progressive MS by relating changes in these brain regions of interest to changes in disability levels and to changes in cognitive abilities. Pursuing this research can further help evaluate the effectiveness of Ibudilast, the treatment under study in the trial, for progressive MS. Even if this therapy is determined to not be effective in MS, evaluating these measures will help determine the length and number of patients needed for future MS clinical trials. There are several impactful patient-related outcomes that may result from this research and could come within the first year of initiating the project. The long-term impact of this proposal is to accelerate evaluation of treatments for progressive MS, meeting perhaps the most significant unmet need in MS treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810372
Entities
People
- Eric Klawiter
Organizations
- Massachusetts General Hospital
- United States Army