Because people with MS experience the disease in so many different ways, some MS investigators wonder whether MS has a single cause, and whether a single therapy will be found to work for all those who have it. The possibility of multiple causes of MS was the focus of the path-breaking international collaboration known as The MS Lesion Project, funded through the Society’s Promise: 2010 Initiative.
Disease activity and symptoms vary greatly among people with MS. In 1998 the National MS Society convened a task force to discuss whether looking at lesions — that is, areas of brain tissue where myelin has been stripped from nerve fibers — would reveal why people experience the disease so differently. The task force noted that this issue was of prime importance, and ripe for development, and recommended a targeted research initiative to investigate it. Understanding lesion patterns can provide more information about differences in disease between individuals, which will enable doctors to make more accurate diagnoses, prognoses, and treatment decisions.
Claudia F. Lucchinetti, MD (Mayo Clinic and Foundation) and collaborators from the U.S., Germany and Austria were chosen to conduct this study for their groundbreaking contributions in this area. They amassed a large collection of tissue samples from people with MS — a painstaking effort, because these are obtained through brain biopsies (a rare procedure) or autopsy.
Using samples of brain tissue from MS patients, the team found four distinct types of lesions (patches of disease activity and damage), which differed in the pattern of damage to myelin (the substance that insulates nerve fibers) and in the activity of immune cells and immune proteins. The team sought a way to detect the patterns non-invasively, such as with MRI (magnetic resonance imaging) scans or blood work, and whether the patterns predict different disease course or response to specific therapies.
- The team evaluated previously biopsied people with MS and their database grew to more than 1000 patients. The team classified hundreds of cases in the database to one of the four lesion patterns identified in their research preliminary to this project.
- In collaboration with Howard Weiner, MD (Harvard School of Medicine), samples from 62 people were examined for antibody reactivity using novel microarray (gene chip) technology. Dr. Weiner’s team found that unique antibody patterns were associated with different lesion patterns. Previous research suggested that people with one of these patterns respond to plasma exchange therapy – a treatment used occasionally to treat individuals experiencing severe MS attacks that do not respond to standard steroid therapy. This suggests that in the future, a non-invasive blood test may be able to distinguish an individual’s underlying pathology and help with treatment decisions.
- The team analyzed more than 2467 MS lesions in 106 autopsies of people with MS and 19 biopsies, and verified that active areas – where tissue damage is ongoing – predominate in early MS but are rare in progressive stages. The lesion patterns established early in the disease to persist into later phases if myelin is still undergoing damage.
- Examining the degree of immune T cell-driven inflammation in early MS lesions, the team found a similarity in the extent of inflammation regardless of the extent of active myelin damage. This contradicts the thinking that active lesions contain more inflammation, and indicates that damage to myelin may release additional immune proteins or cells beyond T cells that contribute to inflammation.
- In a study of 67 samples from MS autopsies and 28 controls, the team found a close association between inflammation and nerve cell degeneration in all stages of MS.
- The team earned a grant from the NIH to use their database to study damage to the cortex in MS, and how this damage may specifically impact MS.
Brain tissue samples are essential to efforts such as this. Read more about how to participate in such research.
Read about the outcomes of the entire Promise:2010 initiative in an article from the Summer 2010 issue of Momentum. (.pdf)