Broad rim lesions identified as MS disease progression marker
Study ties wider rims around cells to faster progression
Wider rims of immune cells surrounding multiple sclerosis (MS) lesions in the brain and spinal cord are associated with faster disease progression, a new study shows.
Monitoring this type of lesion may help track MS disease progression and measure how the disease is responding to treatment, and the findings may help guide the development of new strategies for MS therapy, the researchers said.
“This discovery allows us not only to identify patients who need more aggressive treatment earlier but also to evaluate the effectiveness of new drug candidates by observing changes in lesion rims,” Laura Airas, MD, PhD, co-author of the study and a neuroimmunology professor at the University of Turku in Finland, said in a university news story.
The study, “Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis,” was published in Nature Medicine.
MS is caused by inflammation that damages healthy tissue in the brain and spinal cord (collectively called the central nervous system). Regions where such inflammation causes nerve tissue damage are known as lesions.
Lesions and disease progression
Tracking lesions in routine MRI scans is one of the main ways that clinicians and scientists look at disease progression, but it has become increasingly clear that not all lesions affect MS disease progression in the same way.
For the study, scientists analyzed the disease courses of 186 people with MS from the Finnish MS registry who had donated their brains for research after death. Twenty-nine of them had very rapidly progressing disease that led to severe disability in a relatively short time, whereas 33 had very slowly progressing disease that didn’t cause much disability for many years.
The researchers looked at the brains of those two groups of patients. Each MS lesion consists of a spot of damaged nerve tissue. Some lesions are active and have ongoing inflammation. Others have damage to the myelin sheath, which is the target of the inflammatory attack in MS, and to nerve tissue, but are no longer active.
There are also lesions that show evidence of sustained inflammatory activity over time. These are generally identified by a rim of immune cells called myeloid cells. These cells are different from the immune cells that cause active inflammation in MS and available therapies have limited effects on them.
The researchers noticed that some of these lesions had very broad rims around them, with widths upwards of one millimeter. For context, the rim around a typical chronic, active lesion is less than half a millimeter wide.
The lesions with wide rings of myeloid cells, which the researchers termed broad rim lesions, or BRLs, were notably more common among patients who had very rapidly progressing disease: 11 of 17 patients with very rapid progressing MS had at least one BRL, whereas only one out of 26 patients with very slowly progressing MS had BRLs.
“We identified MS lesions with a broad rim of myeloid cells as a hallmark of rapid disease progression in a subset of patients,” the researchers wrote.
The team noted, however, that some patients with fast disease progression had no BRLs, which they said suggests that “other mechanisms might drive progression in a sizeable portion of cases.”
“In the future, it will be critical to prospectively determine these distinct [disease mechanisms] in individual patients using advanced imaging technologies in combination with other biomarkers,” the scientists said.
After the analysis of postmortem samples, the researchers analyzed data from PET scans of 114 people with MS who were still alive. From the PET scans, they were able to identify BRLs in some of the patients’ brains — implying that it is possible to identify this type of lesion in living people.
The scientists found that patients with at least one BRL tended to have more lesions overall. They also were more likely to experience walking difficulty within 12 years of diagnosis, implying a faster progression of disability than was seen in patients without BRLs. These data suggest that BRLs are a new marker of fast disease progression in MS, the researchers concluded.
Data from nine patients who were treated with the approved MS treatment Tysabri (natalizumab) showed that five of the patients experienced a reduction in BRL numbers after a year of treatment. By contrast, four out of nine untreated patients experienced increases in BRL counts over time.
The data also suggest that treatments to target the myeloid cells in BRLs might be important for slowing disease progression in MS, according to the scientists.
“Patients [with BRLs] could benefit from pharmacological treatments targeting the innate immune response in myeloid cells, a therapeutic target that is not adequately addressed by current treatment options,” the team wrote.
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