Research project of the University of Basel and the University of California San Francisco published in “JAMA Neurology”.
Basel / San Francisco, 6th November 2023
Neuroscientists of the EPIC-Team (Expression, Proteomics, Imaging, Clinical) at the University of California San Francisco (UCSF) led by Ahmed Abdelhak, MD, and of the Swiss Multiple Sclerosis Cohort (SMSC) of the University of Basel under the leadership of Professor Jens Kuhle have conducted a study in multiple sclerosis (MS) patients that demonstrates that injury to the central nervous system can be detected up to 26 months before deterioration of neurological functions manifests clinically. The results of this study will be published in the renowned journal "JAMA Neurology" on November 6, 2023.
Neurofilament Light Chain (NfL) levels in the blood is a specific biomarker for damage of nerve cells and has been established earlier for monitoring acute disease activity and the efficacy of therapy. However, there was no biofluid marker defined that associates with continuous worsening of neurological functions, called 'progression', that occurs despite optimal therapy in most MS patients. The key finding of this study is that increased levels of NfL prognosticate progression in a period when it cannot be diagnosed with current clinical tools. This advance in early detection of disease course opens new treatment windows and better management of MS.
The study conducted by UCSF and University of Basel researchers aimed at addressing the current diagnostic gap in predicting disease progression in MS by analyzing long-term data from nearly 13,000 patient visits and blood samples. "The result that blood levels of NfL can prognosticate disease progression up to more than two years in advance of the occurrence of clinical manifestation of symptoms is a game changer for how we can monitor and manage the treatment of MS patients: it provides crucial rational for early therapeutic interventions," said Ahmed Abdelhak, the first author of the study.
The study demonstrates that NfL concentrations increase sharply between 12 and 26 months before the diagnosis of confirmed disability progression is made. Once the disability becomes clinically evident, NfL concentrations are no longer elevated compared to patients with stable disease, suggesting that this biomarker shows dynamic changes indicative of actual disease processes. This suggests that NfL measurements indicate underlying nerve injury earlier than physical examinations of neurologists. Overall, these findings can help doctors and clinicians identify patients who are at high risk of progression and provide early therapeutic intervention to contain disease progression.
Relevance for MS-Research
This study combines two of the largest and best documented MS cohorts worldwide. It builds on earlier work conducted by researchers from the University of Basel that were published in February 2022 and September 2023 in “Lancet Neurology”. The Swiss researchers demonstrated therein the added value of NfL as a blood biomarker for assessing the disease activity state of MS patients by establishing normative data for this biomarker in adults and children that allows to qualify NfL concentrations as normal or increased.
„Besides the groundbreaking insights regarding the temporal link between NfL elevation and disease progression in MS, the study reinforces the pivotal role of NfL as an early marker of neuronal injury. Monitoring NfL levels has already been established as an important indicator to detect concurrent disease activity with higher sensitivity than a clinical examination or conventional MRI scans. The current study further stresses the critical value of NfL measurement for a more personalized medical treatment”, says Professor Jens Kuhle.
The focus of future studies is how the new insights on what increased NfL means can be translated into better treatment algorithms.
Relevance for MS Patients
Nearly three million people worldwide suffer from MS. Every progress in the understanding of this disease has the potential to improve therapy efficacy, and hence the lives of patients as well as their families. Early and precise detection of prospective damages opens new windows of early therapeutic intervention. The therapeutic target is to hold NfL concentrations at levels of healthy persons.
