[FG] Kühne Michael

Research Focus

Neurology

Area of Research

Translational Medicine research in the field of inflammatory and degenerative diseases of the Central Nervous System (CNS), with a focus on multiple sclerosis and related diseases 

Clinical research on patient prognosis and outcomes within the Swiss Multiple Sclerosis Cohort Study (SMSC)

Pragmatic Trialing and Real-World Evidence

Approved Research Projects

• Swiss Multiple Sclerosis Cohort-Study (SMSC, supported by the Swiss MS Society)
• 'Towards development of neurofilament light chain as precision medicine biomarker for multiple sclerosis' (Swiss National Science Foundation project 320030_189140 / 1, 2019-2023)
• 'Quantifying progression in multiple sclerosis: serum glial fibrillary acidic protein (sGFAP) for personalized medicine and identification of novel targets' (Swiss National Science Foundation project 320030_212534 / 1, 2023-2027)
• Personalized medicine in Multiple Sclerosis pRagmatIc Platform Trial (MultiSCRIPT) (Swiss National Science Foundation, IICT call 2022; Applicants: PD Ö Yaldizli (PI), PD R Hoepner, PD L Hemkens, Prof C Zecca, Prof J Kuhle; 2022-2026)
• Definition of novel biomarkers of disease activity, therapy response and diagnostic specificity in other CNS diseases (neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), amyotrophic lateral sclerosis (ALS), and cardiovascular diseases/stroke

Collaborations

National Collaborations

• SMSC consortium (SMSC; MS Centres in Swiss University Hospitals (Basel, Bern, Geneva, Lausanne, Zurich) and Cantonal Hospitals (Aarau, Lugano, St. Gallen))
• Department of Biomedical Engineering (Prof. C. Granziera, Basel)
• Memory Clinic, Department of Geriatric Medicine, Felix-Platter Spital, University of Basel (PD Dr. M. Sollberger)
• Prof. Paul G. Unschuld, Médecin-chef du Service, Service de Psychiatrie Gériatrique, Hôpitaux Universitaires de Genève (HUG)

International Collaborations

• University of California, San Francisco (USA)
• University of Münster (Germany)
• University of Oxford (UK)
• University of Turku (Finland)
• Karolinska Institutet Stockholm (Sweden)
• University of Verona (Italy)
• Vita-Salute San Raffaele University, Milan (Italy)
• Fondazione Mondino, Istituto Neurologico Nazionale a Carattere Scientifico, Pavia (Italy)
• University of Sydney (Australia)
• Tianjin Medical University (China)

Ongoing Research Projects

The better understanding and treatment of MS needs prospective, standardized, and high-quality MRI and clinical data from large patient cohorts to allow for development and validation of biomarkers on the individual patient level, and hence application in clinical practice as Precision Medicine tools. The SMSC, initiated in 2010, established in 2012 and coordinated by the MS Centre Basel (PI Jens Kuhle) since then, is the mainstay of research efforts in our research group in the Department of Clinical Research and the Department of Biomedicine (Clinical Neuroimmunology); it provides an internationally unique long-term follow-up of over 1700 Swiss MS patients with clinical and MRI data, and blood and cerebrospinal fluid samples for research. The SMSC provides access to a population of MS-patients in all stages and states of disease, treated with all state-of-the-art therapies. The close collaboration with the Translational Imaging in Neurology (ThINk) group at the Department of Biomedical Engineering enables characterization of patients with cutting edge neuroimaging techniques.

We are an integral part of the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) that coordinates and supports several competitively funded research groups, dedicated to improving the clinical, imaging, biochemical, molecular, and cellular characterization of the disease process and understanding the benefits and side effects of newly developed therapies. We aim at exploring and validating new diagnostic tools for patients with neurological diseases. By integrating basic research work on the pathophysiology of biomarkers, with data from large size patient cohorts (real-world and clinical trials) we develop biomarkers to practical clinical application with the goal of better therapeutic decision making in individual patients ('personalized medicine').

Neurofilament light chain (NfL) has been established as a blood-based precision medicine tool in MS and many primary neurodegenerative diseases (Alzheimer's disease, ALS, among others). We have spearheaded its establishment in MS as a marker of a) disease activity, b) drug response, and c) as predictor of the long-term outcome of disability and brain atrophy. Within a Swiss National Science Foundation project, we pursue to establish NfL as a diagnostic tool for individual patients for therapeutic decision making.

In collaboration with a network of imaging researchers at the Department of Neurology Basel and national (SMSC Study consortium) and international (UCSF, University of Münster, University of Oxford) research centres we have achieved:

1. to characterize the pathophysiology of NfL by elucidating its metabolism and pharmacokinetics (collaboration with University of Oxford)
2. to establish a normative data base from controls over eight decades of age as a reference (international collaboration: Germany, Switzerland, United States; as well as for paediatric medicine)
3. to establish the correlation of NfL with novel MRI features relating to MS progression (investigation on the relationship between serum NfL and chronic active lesions (phase rim lesions, slowly expanding lesions) in MRI as well as their combined value for treatment response and clinical outcome prediction in MS patients (collaboration with Prof. C. Granziera, Basel)

Together with the Department of Biomedical Engineering (Prof Cristina Granziera, ThINk Basel) and the Department of Clinical Research we are evaluating and validating manual and automated technologies for the meanwhile more than 10 000 cranial MRI scans acquired within the SMSC. We are applying these technologies and are generating high quality MRI data characterising this large real-world cohort further. 

Glial fibrillary acidic protein (GFAP) is an astrocyte-specific biomarker whose increase in blood reflects the "sclerosis" (astrocyte proliferation) part of MS pathogenesis. We have found that the combination of NfL and GFAP measurement has now become the promising prognosticator of disability worsening, and of drug response in MS on the group level. We aim now for extension and validation of our results in large and longitudinal cohorts of patients, and the establishment of normative values for GFAP, to allow the individual use in routine clinical practice.

NMOSD and MOGAD have been recognized in the past years as disease entities distinct from MS in pathophysiology, long-term course and therapy, while the clinical phenotype shows strong overlap and makes diagnosis difficult, specifically in acute presentations. We have established granulocyte activation markers as a novel diagnostic tool that allows differential diagnosis of NMOSD and MOGAD vs MS with equal accuracy as with current diagnostic gold-standards, but with the perspective of a same-day turnaround of test, preventing deleterious delay of therapy. A large-scale international collaboration is under way to validate markers for the differentiation of NMOSD vs MOGAD, and assay platform applicable in clinical laboratory settings.

Further, we investigate other biofluid markers by several proteomic platforms to contextualise established biomarker signals with regard to state and stage of MS, and for differential diagnosis vis-à-vis other inflammatory neurological diseases.

These projects are based on patient information and biological samples from the SMSC, and international collaborations in Europe the Northern Americas and Asia.