Research Group Jens Kuhle
Area of Research
Translational research in the field of inflammatory degenerative CNS diseases, in particular multiple sclerosis. Swiss Multiple Sclerosis Cohort Study (SMSC)
Approved Research Projects
- Swiss Multiple Sclerosis Cohort-Study.
- Axonal biomarkers in blood samples of Multiple sclerosis and patients with other neurological diseases.
- Serum Neurofilaments in Stroke.
- NfL Bestimmungen bei Patienten mit Arteriendissektion und intrazerebralen Blutungen.
- Quantifying axonal injury in patients with Multiple sclerosis.
- Swiss Multiple Sclerosis Cohort-Study.
- Assessing axonal injury in body fluids of MS patients.
- Towards quantifying neurodegeneration in blood samples from Multiple sclerosis and patients with other neurological diseases.
- Neurofilament light chain in Multiple Sclerosis.
- Analysis of serum neurofilament light chain in sporadic cerebral small vessel disease.
- Plasma NfL in relapsing MS.
- Validation of an assay for serum NfL in MS.
- Analysis of Serum Neurofilament Light Chain (NfL) in Blood from Multiple Sclerosis patients: towards establishing a drug response and prognostic biomarker in serum.
- Towards quantifying axonal injury in blood samples from patients with Multiple Sclerosis.
- Prediction of conversion to MS by blood-based biomarkers.
- Neurofilament quantification in longitudinal blood samples from patients with MS.
- Analysis of Serum NfL in blood samples from progressive MS.
- Analysis of biomarkers of neurodegeneration from clinical phase 2 and 3 Trials.
- Analysis of serum and plasma NfL from a large observational MS Cohort.
- Blood NfL measurements by ultrasensitive Simoa assay
- Neuroaxonal injury in Clinically Isolated Syndromes: neurofilament light chain in REFLEX
- Measures of astrocytic damage in a large cohort of SPMS patients
- Swiss MS Cohort Study consortium
- Department of Biomedical Engineering (Prof. C. Granziera, Basel)
- Medical Image Analysis Centre Basel (Lead Dr. J. Wuerfel)
- University of California, San Francisco (USA)
- University of Münster (Germany)
- University of Oxford (UK)
Ongoing Research Projects
The strategic goal of our work is a translational medicine approach by integrating basic research work on the pathophysiology of biomarkers, specifically on NfL, with data from large size patient cohorts (real-world and clinical trials) in view of a clinical application of biomarkers for precision medicine.
NfL has been established as a blood-based precision medicine tool in MS and many primary neurodegenerative disease (Alzheimer's disease, amyotrophic lateral sclerosis, among others). We were frontrunners in establishing NfL in MS as marker of a) disease activity, b) drug response, and c) as predictor of the long-term outcome of disability and brain atrophy on the group level. These activities are mainly ongoing in the premises of the DBM with strong statistical/analytical support by the Clinical Trial Unit at the DKF.
Within a Swiss National Science Foundation project, we pursue now 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 (Swiss MS Cohort Study consortium) and international (UCSF, University of Münster, University of Oxford) research centres we pursue the following 4 subprojects:
a) to characterize the pathophysiology of NfL by elucidating its metabolism and pharmacokinetics (collaboration with BioZentrum mass spectrometry facility, University of Oxford).
b) to establish a normative data base from controls over eight decades of age as a reference (international collaboration: Germany, Switzerland, United States)
c) to establish blood-based biomarkers characterising demyelination/remyelination (international collaboration) and microglial/glial activation in MS to contextualise NfL signals in stages (relapsing-remitting vs progressive) and states (acute exacerbation vs stable disease phase) of MS
d) 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)
This project is based on three sources of patient information and biological samples established in the course of the past eleven years:
1. Swiss MS Cohort Study: Comprehensive and prospective follow-up of >1200 MS patients with standardized clinical assessment by certified raters and 6/12 monthly follow-up, with biosample collection and state of the art MRI assessment.
2. A biobank of more than 2500 neurological patients processed and stored according standard procedures including aliquoted cerebrospinal fluid, serum, plasma, DNA samples with extensive clinical and paraclinical information from MS and non-MS patients including clinical and paraclinical follow-up.
3. A biofluid reference data sets of 13'000 normal control persons; world-leading expertise in high-sensitivity biofluid analysis (blood and CSF), and assay development.
Financial support is provided by the Swiss National Science Foundation and through third parties in the course of biomarker projects.
Together with the Department of Biomedical Engineering (Prof Cristina Granziera; SNF professorship on advanced imaging), Medical Image Analysis Centre Basel (Lead Dr. J. Wuerfel), and the CTU Basel we are evaluating and validating manual and automated technologies for the meanwhile more than 4500 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.
As a result of the collaboration across academic centres in Switzerland, several scientific projects within the SMSC and in close collaboration with the CTU Basel (Dr P. Benkert/ S. Schädelin, MSc) are ongoing and a number are now close to finalization. Besides the focus on further developing NfL and related biomarkers towards clinical application, these are examples of projects currently under way:
a) investigations on MS disease progression independent of relapse activity (PIRA), and effects of disease modifying drugs,
b) the prognostic relevance of early CSF profiles on future disease activity and long-term severity outcomes,
c) the assessment of digital data in MS for prediction of later disease course further, and
d) the value of measuring evoked potentials to predict future outcomes and their potential utility as endpoints for clinical trials