Prediction of Future Disability in MS Using Combined Novel MRI and Serological Markers
Abstract
In line with the MSRP IIRA focus area of biological correlates of disease activity and progression in MS, we propose to study novel imaging and blood markers of damage in people with Multiple Sclerosis (MS) as predictors of future disability. The course of MS is very variable among individual people with MS, who can eventually develop little disability or much disability. We believe that the nervous systems ability to withstand and repair damage dictates, at least partially, the degree of future disability that develops. Unfortunately, we cannot now reliably predict the long-term outcome. Current available predictors of disability do not apply well to individual patients and seldom help in the choice of treatment. Fortunately, we have an ever-increasing choice of medications to treat MS. Each medication has a unique risk/benefit profile, making it a crucial task to successfully balance the effectiveness and risk of the medication to match the perceived aggressiveness of each patients MS disease. We propose to test innovative imaging (a type of MRI) and measurements of proteins in blood as markers of MS aggressiveness. We wish to determine if these novel markers can be used to better predict, in individual patients, future course of disease. Knowing the future course of disease would ultimately be used to guide treatment choices. Gradient Echo Plural Contrast Imaging (GEPCI) is a novel MRI method that measures the amount of damage in different regions of the brain in MS. GEPCI can be performed on any standard clinical MRI machine in under 10 minutes (under 5 minutes using newer technology). It does not require contrast administration. Neurofilament light chains (NfL) are markers of damage in the brain and are increased in the spinal fluid of many people with MS. Recent technological advances have allowed for NfL to be reliably measured in the blood, making the test potentially easy to perform on many people with MS. At our center, for many years, we have been studying GEPCI in MS patients. We now have a group of people with MS with available GEPCI MRI data going back 9 years. In addition, many of these same people with MS have frozen stored blood samples from years ago. We will test how well GEPCI-measured brain damage and blood NfL levels can predict future disability in these MS patients. We will incorporate these two markers into a statistical model that also includes other pertinent disease and patient factors and evaluate that models ability to predict future disability. To achieve this, we will re-analyze previous MRI data and measure levels of NfL on previously stored serum (blood) samples and we will ask all of the subjects to return for one follow-up visit to undergo clinical neurologic assessment. This proposed research study will allow the testing of these novel MRI and blood markers on a number of people that have, on average, a long interval between the date of the MRI and/or blood collection and the date of their new clinical assessment. Results of this proposal can be applied to all MS patients when important treatment decisions are being made, but perhaps especially to those with early MS. These MRI and blood markers could easily be applied in the clinic using a fast MRI protocol on standard MRI scanners, and on standard blood samples. If this proposal is successful, we foresee it having a direct clinical impact by being applied in daily practice. Patients with a potentially aggressive disease course based on these markers might be recommended to use stronger (but potentially riskier) treatments, whereas those with markers that predict a mild course could be advised to use safer but less strong options. Results of our study may need to be replicated in other cohorts but, given the availability and reliability of the methods behind the MRI and blood markers, our results can quickly be adopted in clinical practice and have an impact on how physicians can for people with MS. We do not anticipat
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910820
Entities
People
- Dorothy Cross
Organizations
- United States Army
- Washington University in St. Louis