Immunology

Microglia: pathology and pathway

Microglia are presented as key regulators of CNS immunity and major drivers of smouldering MS pathology. By imaging and therapeutically modulating these cells, new avenues are opened to better predict, and potentially slow, disease progression.

In this keynote from Athens, Professor Laura Airas presents the central role of microglia in multiple sclerosis pathology and progression, with a focus on how these cells can both protect and damage the CNS. The presentation reviews microglial biology, their contribution to smouldering MS lesions, and how advanced imaging, especially TSPO-PET, can visualise microglial activation in vivo. Emerging therapeutic strategies, including BTK inhibitors and repurposed agents, are discussed as potential ways to modulate microglia and slow progression.

Key Insights from the Lecture:

Microglia are described as long-lived, self-renewing innate immune cells of the CNS, involved in surveillance, synaptic pruning, debris clearance and repair.
A shift from homeostatic to pro-inflammatory phenotypes is highlighted as a key driver of neurodegeneration and progression in MS.
Chronic active (“rim”) lesions are presented as a hallmark of smouldering pathology, characterised by dense rims of activated, iron-laden microglia.
TSPO-PET imaging is shown as the current reference technique to quantify microglial activation in vivo, revealing increased binding in SPMS and in chronic active lesion rims.
High TSPO signal is reported to correlate with brain atrophy, microstructural white-matter damage, fluid biomarkers (e.g. NfL, GFAP, CHI3L1) and future clinical progression.
Age-related “inflammaging” of microglia is described, with MS brains exhibiting a microglial activation profile comparable to older healthy controls.
Microglia are presented as therapeutic targets, with BTK inhibitors and repurposed drugs such as hydroxychloroquine under investigation to shift microglia towards a more homeostatic state.
Translational opportunities are highlighted across neurology and psychiatry, where aberrant microglial activation may contribute to cognitive decline and other CNS symptoms.

“Microglia: pathology and pathway “.

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About the speaker:

Laura Airas

Professor of Neuroimmunology at the University of Turku

Neurologist Laura Airas is Professor of Neuroimmunology at the University of Turku, Finland, where she also obtained her MD. After graduation, and then completing her PhD on immunology and cell biology, she specialized in neurology, obtaining a neurology consultant status in 2001 and the title of docent in neurology in 2007.

She founded her own research group in 2002, studying the immunology of pregnancy in MS. Currently, she leads a research group to develop treatments for neuroimmunological diseases where no effective treatments are yet available, such as progressive MS. The group’s main aim is to elucidate the pathological mechanisms of progressive MS by using a multi-modal approach which includes PET, advanced MRI, and soluble biomarker analysis.

Professor Airas is an experienced clinician, and well connected with scientists of different backgrounds. She spends half of her professional time as a clinical neurologist, consulting for MS patients, while also actively participating in research and clinical trials for MS.

Laura Airas has authored over 100 peer-reviewed articles in international journals. In 2015 she received an international Grant for Multiple Sclerosis Innovation award, and in 2016–2017 she spent an academic year as a visiting professor at Yale University, Connecticut, USA.