Prof Laura Airas is based in Turku PET Centre, Turku, Finland and writes about their recent paper.
She has received honoraria from Biogen, Roche., Genzyme, Merck Serono and Teva, and institutional research grant support from Finnish Academy, Sigrid Juselius Foundation, Nancy Davis Foundation, Biogen, Genzyme, Merck Serono and Novartis.
Brain microglial activity predicts faster progression of MS
Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis.Sucksdorff M, Matilainen M, Tuisku J, Polvinen E, Vuorimaa A, Rokka J, Nylund M, Rissanen E, Airas L.Brain. 2020 Oct 2:awaa275. doi: 10.1093/brain/awaa275.
A study conducted at the National Turku PET Centre, Turku, Finland, found that higher microglial cell activity in areas surrounding the focal inflammatory lesions in the brain predicts a faster progression of MS disease. It is the first study to show that the active innate immune cells in the brain predict progression of MS.
There are a number of effective drugs to prevent the exacerbations associated with relapsing-remitting MS, but yet there is no medication that would efficiently prevent the steady worsening associated with the disease. The pathological processes associated with the progressive forms of the disease take place behind the blood-brain barrier in the brain, and affecting these processes is challenging.
– First of all, it is difficult to accurately examine the brain in living patients. Following this, the mechanisms leading to neuronal degeneration are poorly understood. Due to this, it is difficult to directly slow down the neural degeneration process in any brain disease. An effective drug also needs to get through a tight blood-brain barrier, and developing a drug capable of this has its own challenges, explains Professor Laura Airas from the University of Turku.
The study was able to predict the disease progression with 95% accuracy
Neuropathological studies have identified an inflammatory reaction outside of focal inflammatory lesions in the brain of patients with progressive MS. Such diffuse brain inflammation, which sweeps across the entire brain tissue, is thought to be one of the factors contributing to chronic degeneration of the nervous system in MS and other degenerative diseases of the central nervous system.
Diffuse inflammation involves the harmful activation of the brain innate immune cells, microglial cells, which can be measured using positron emission tomography (PET) imaging, but not conventional MRI.
In a study conducted at the National Turku PET Centre, the link between microglial cell activity to later disease progression was modeled by stepwise logistic regression analysis. This model tested 21 different factors potentially contributing to disease progression, and of all these factors the microglial activity measured using PET imaging was recognized as the most significant.
— Regardless of relapses, the model predicted disease progression with 95% accuracy. The study carefully controlled for confounding factors such as medication, sex, age and duration of the disease, Airas says.
The findings are from an extensive dataset of 69 MS patients and 18 healthy controls. All subjects underwent an initial MRI and a TSPO-PET scan of the brain using a microglial cell binding radioligand [11C]-PK11195. The clinical severity of the disease was assessed using EDSS scoring, both at baseline and after an average of four years follow-up.
— This is the first study to show that the active, TSPO-PET detectable phenotype of microglial cells predicts progression of MS. The study proves the harmful nature of that particular microglial cell type. It demonstrates that PET imaging, with its molecular-level specificity, is a powerful research tool to investigate specific aspects of brain pathology in vivo. Importantly, it allows linking a given brain cell phenotype to the clinical status of the patients.
TSPO-PET imaging has excellent potential to be used as a biomarker in drug development targeted for progressive MS disease in the future.
The study was published in the distinguished journal Brain: https://doi.org/10.1093/brain/awaa275
For more information, please contact: Laura Airas Professor of Neuroimmunology, University of Turku, +358 50 3294321, firstname.lastname@example.org