Aims of the work

The major goal of research in the Neuroinflammation lab is to understand the pathobiology of multiple sclerosis and other neuroinflammatory and neurodegenerative diseases using in vivo imaging methods – particularly positron emission tomography (PET) and magnetic resonance imaging (MRI). Airas lab develops and performs clinical studies with new PET radiotracers and MRI techniques, on state-of-the-art imaging equipment housed at Turku PET Center. The aim of the work is to elucidate the pathological processes ongoing in the CNS of progressive MS patients, and to explore how the in vivo detectable abnormalities relate to clinical disability. Additional goals of the research are to adapt new imaging techniques as biologically and clinically relevant outcome measures in both clinical trials and routine patient care. The main focus of the research is progressive multiple sclerosis where there is a great unmet therapeutic need, but the new imaging methodology can also be applied to other inflammatory and neurodegenerative diseases of the CNS.

 

Current research activities

Multiple sclerosis research is focusing on evaluation of smoldering, diffuse innate immune system activation in progressive multiple sclerosis brain. This is evaluated using TSPO-binding radioligands, and a radioligand ¹¹C-SMW139 binding to P2X7 molecule expressed on proinflammatory microglia and macrophages. Impact of innate immune cell activation on synaptic density is being investigated by using a combination of a TSPO-binding radioligand and ¹¹C-UCB-J, a radioligand binding to SV2 synaptic protein. The PET studies are complemented by advanced MRI imaging and soluble biomarker analysis, and careful clinical evaluation of the patients for comprehensive understanding of the ongoing neuropathology.

Main results of previous studies

We are among the first in the world to demonstrate in vivo an increase in innate immune system activation in progressive multiple sclerosis normal appearing white matter compared to RRMS and healthy controls. We have demonstrated that innate immune system activation increases with disease progression, and can be targeted therapeutically in a TSPO-PET-measurable way. We also showed that increased microglial activation predicts later disease progression in multiple sclerosis. We have developed an analysis and modelling pipeline for streamlined evaluation of TSPO-PET images, that can be applied to large cohorts of MS patients both in a cross-sectional and longitudinal way both in a real-world setting and in clinical trial context.

Investigators

Principal investigator:

Professor Laura Airas, MD, PhD

Senior investigators:

Eero Rissanen, MD, PhD

Maija Saraste, PhD

Markus Matilainen, PhD

Parisa Hariri, PhD

PhD students:

Marcus Sucksdorff, MD

Marjo Nylund, MSc

Amelie Möck, MD

Sini Laaksonen, MD

Imran Waggan, MSc

Taruliina Parkkali, MD

Olavi Misin, MD

Anna Vuorimaa, MD

Taru Nikkilä, MD

Eero Polvinen, MD

Jouni Tuisku, MSc

MSc students:

Mohammad Kafami Khorasani, BSc

Pihla Miettinen, BSc

Eman Hassanain, BSc

Brittany Du Bose, BSc

Extended medical studies:

Markus Kotka, BM

Eemeli Hiltunen, BM

Research coordinators:

Eveliina Honkonen, MSc

Marjo Nylund, MSc

 

Collaboration

We have wide national and international connections and collaborations with universities and pharma companies in Finland, Europe and the United States. We are affiliated with Neurocenter Finland and the Finnish Academy flagship InFLAMES (Innovation Ecosystem based on the Immune System). The PhD students in the group belong to Turku University Clinical Doctoral Program and the Drug Development Doctoral Program.

 

External funding

Academy of Finland

Sigrid Juselius Foundation

Turku University Hospital Clinical Funds (ERVA)

International Progressive MS Alliance

IIS studies funded by industry

Collaborative projects with industry

 

Completed doctoral theses

Jouni Tuisku, Imaging of neuroinflamation in multiple sclerosis brain. University of Turku, 2021.

Petri Elo, Preclinical evaluation of novel radiopharmaceuticals for positron emission tomography imaging of animal models of multiple sclerosis. University of Turku, 2020.

Maija Saraste, Pregnancy-related immune alterations in multiple sclerosis. University of Turku, 2018.

Eero Rissanen, Imaging Neuroinflammation in Progressive Multiple Sclerosis. University of Turku, 2015.

Anna Jalkanen, Multiple sclerosis and pregnancy: clinical and immunological aspects. University of Turku, 2014.

Teemu Paavilainen, Magnetic Resocance Imaging Methods in the Follow-up of Multiple Sclerosis and in Farby Disease. University of Turku, 2013.

 

Selected publications

Sucksdorff M, Matilainen M, Tuisku J, Polvinen E, Vuorimaa A, Rokka J, Nylund M, Rissanen E, Airas L. Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis. Brain. 2020 Dec 5;143(11):3318-3330. doi: 10.1093/brain/awaa275. PMID: 33006604; PMCID: PMC7719021.

Bezukladova S, Tuisku J, Matilainen M, Vuorimaa A, Nylund M, Smith S, Sucksdorff M, Mohammadian M, Saunavaara V, Laaksonen S, Rokka J, Rinne JO, Rissanen E, Airas L. Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging. Neurol Neuroimmunol Neuroinflamm. 2020 Mar 2;7(3):e691. doi: 10.1212/NXI.0000000000000691. PMID: 32123046; PMCID: PMC7136049.

Saraste M, Bezukladova S, Matilainen M, Tuisku J, Rissanen E, Sucksdorff M, Laaksonen S, Vuorimaa A, Kuhle J, Leppert D, Airas L. High serum neurofilament associates with diffuse white matter damage in MS. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 8;8(1):e926. doi: 10.1212/NXI.0000000000000926. PMID: 33293460; PMCID: PMC7803327.

Bodini B, Tonietto M, Airas L, Stankoff B. Positron Emission Tomography in Multiple Sclerosis: Straight to the Target. Nat Rev Neurol. 2021. In press.

 

Click here for complete list of publications

 

More information can be found from the web page of Airas group (in progress)