University of Verona, Italy: meningeal inflammation and cortical pathology

Can the degree of meningeal inflammation and cortical pathology be used to stratify early progressive MS patients?

Principal Investigator: Massimiliano Calabrese, M.D., Ph.D.
Institution: University of Verona
Country: Italy
Amount Awarded: €68,673

This team has previously shown that the amount of damage to the grey matter on the surface of the brain in early stages of MS associates with an increased chance that the future disease course will be more severe. Now they are analyzing the cerebrospinal fluid that surrounds the brain and using MRI brain scanning to examine brain tissue from people with progressive MS obtained via autopsy. They are examining types and quantities of messenger proteins and molecules that may be associated with damage seen by MRI scanning. This combined approach may identify both the molecules and brain imaging signals that predict a more severe disease, so that neurologists can recognize and address a more severe course of MS before quality of life is severely affected.

What does this mean for people living with progressive MS?

Being able to address and vigorously treat a severe course of MS as early as possible is crucial to stopping progression in its tracks.

Project Update

Status: Completed

This research team developed a new combination of MRI sequences for a ‘3T MRI scan’, specifically designed to assess grey matter damage in the brain. They used this to classify people with progressive MS into two groups, based on the volume of cortical lesions. The researchers evaluated relevant proteins in the cerebral spinal fluid of people in these two groups and found that the two groups had a different protein profile. The group with a higher volume of cortical lesions had significantly higher levels of lymphoid chemokines, as well as other molecules associated with causing inflammation in the brain. The group with a lower volume of cortical lesions had significantly higher levels of molecules that slow down inflammation. The researchers also looked at brain tissues that had been donated by of people with secondary progressive MS who had passed away. In cases with a high degree of meningeal inflammation (inflammation of the membranes covering the brain and spinal cord) they found increased gene expression levels of inflammatory cytokines/chemokines in the  meninges. They also found significantly higher levels of pro-inflammatory molecules in the cerebral spinal fluid. In cases with a low degree of meningeal inflammation, the researchers only detected increased levels of the  regulatory molecule IL-4 in the cerebral spinal fluid. By classifying people with progressive MS based on the volume of cortical lesions and the level of brain atrophy, the researchers identified two subgroups with different  clinical and neurophysiological features and specific cerebral spinal fluid molecular profiling. This may be a useful approach for grouping people with MS which could help identify new therapeutic targets to prevent/block  disease progression.

Principal Investigator Massimiliano Calabrese

Massimiliano CalabreseMassimiliano Calabrese is a neurologist who leads the Advanced Neuroimaging Lab of the Neurology Section, University Hospital of Verona. After graduating in Medicine and Surgery at Padua’s University, Dr. Calabrese completed his residency in Neurology with honors at the first Neurology Clinic of the same University (specialization thesis focused on “Regional Cortical Atrophy in Multiple Sclerosis”). He also completed a fellowship at the Neuroimmunology Branch of National Institute of Health in Bethesda (Chairman Prof. Henry McFarland and Dr. Roland Martin). In January 2013 he moved to the University of Verona to develop and expand his research focused on neurodegeneration and neuroprotection in Multiple Sclerosis, with the ultimate aim of predicting and of slowing down the accumulation and progression of irreversible disability. His work on grey matter inflammation and neurodegeneration in Multiple Sclerosis has earned more than 60 highly cited publications in international peer reviewed journals and several international awards.

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