Fredrik Piehl Team
Clinical Neuroimmunology and Immunomodulation
About
MS is an autoimmune disease that causes damage to the nerve fibers of the central nervous system (CNS), which is the basis for the permanent neurological disabilities that many patients eventually will develop. In MG autoantibodies disturb the signal transmission between nerve and muscle causing muscle weakness that sometimes can be life-threathening.
Our research
Clinical Neuroinflammation and Neurodegeneration
We work with different inflammatory diseases of the central and peripheral nervous systems. Our main focus is multiple sclerosis (MS), an autoimmune disease affecting the central nervous system (CNS), but also do research in myasthenia gravis (MG), psychiatric conditions and traumatic brain injuries.
Currently we have an incomplete understanding of how inflammation in the nervous system is regulated and what significance it may have for ensuing nerve injury.
Starting from a more experimental approach, our research has now evolved to be mainly clinical. MS is our main focus. Here are objectives are to generate better knowledge of why the adaptive immune system attacks the CNS, what mechanisms are involved, imaging and soluble biomarkers reflecting what is happening and, perhaps most important of all, how we can devise better therapeutic interventions. Our aim is also to address the needs of those affected by MS, and we strive to include our patients as active partners in the research we do. A major line of research is to understand the role of B cells (an immune cell type) in MS, and how this can be translated into treatments with better benefit-risk balance. To this end we examine cells and biofluids, such as serum and cerebrospinal fluid, with advanced methods, but we also study treatment effects and adverse events with epidemiological methods.
Over the last decade we have performed several studies where we compare the effect and safety of rituximab, a B cell-eliminating drug that is approved for rheumatoid arthritis, but not yet for MS. Somewhat surprisingly, our studies show that rituximab in most instances provide a better benefit-risk balance and tolerability compared with MS-approved drugs. These studies have encouraged more extensive use of rituximab so that it is now the most used MS therapy in Sweden, and at substantial cost savings for the health care system.
A problem not resolved, however, is why some people with MS continue to worsen even though we use drugs that strongly reduce inflammation. In order to understand why this happens, we need to understand better the neurodegenerative aspects of MS. To do so we study how the levels of different biomarkers change over time and to what degree our current treatments affect these processes. We also actively participate in clinical trials where novel treatments are tested in a clinical setting. This also includes studies of how non-drug interventions can improve symptoms, such as how physical exercise can reduce MS-fatigue.
Myasthenia gravis (MG) is a neuroinflammatory condition where antibodies block the transmission of signals between nerve and muscle, thereby resulting in muscle fatigue and weakness. Also here B cells play a role, though likely in part different from MS. Fewer approved drug therapies are currently available for MG than MS, and current treatment guidelines are mostly based on empirical evidence rather results from robust trials. However, we have conducted one of the first such trials exclusively in individuals with new onset disease, showing that rituximab started early is associated with improved outcomes. We are now working on several follow up studies to address how the treatment of MG can be further improved.
Together with several collaborating groups we also conduct research in both traumatic and psychiatric conditions, where we contribute with our expertise in biomarkers.
Research Projects
- Experimental clinical studies on neuroimmunology, and imaging and soluble biomarkers in MS, and other inflammatory and non-inflammatory conditions.
- Clinical treatment research in MS.
- Clinical treatment research in MG.
Team leader
Fredrik Piehl, professor, senior physician, fredrik.piehl@ki.se
Team members
Susanna Brauner, senior research specialist, docent, susanna.brauner@ki.se
Simon Englund, project coordinator, PhD student, simon.englund@ki.se
Ann Eriksson-Dufva, PhD student, ann.erikssondufva@ki.se
Filippo Ferro, PhD student, filippo.ferro@ki.se
Linda Forsberg, project coordinator, +46852487402, forsberg.linda@ki.se
Lars Fugger, affiliated to research, lars.fugger@ki.se
Albert Hietala, affiliated to research, albert.hietala@ki.se
Mohsen Khademi, senior lab manager, mohsen.khademi@ki.se
Gavin Li, PhD student, gavin.li@ki.se
Mingming Li, PhD student, mingming.li@ki.se
Roland Martin, affiliated to research, roland.martin@ki.se
Anna Mattsson, laboratory assistant, anna.g.mattsson@ki.se
Tomas Olsson, senior professor, tomas.olsson@ki.se
Andre Ortlieb Guerreiro-Cacais, senior research specialist, docent, andre.ortlieb@ki.se
Cynthia Perez, affiliated to research, cynthia.perez.estrada@ki.se
Malin Petersson, PhD student, malin.petersson@ki.se
Nicolas Ruffin, senior research specialist, docent, nicolas.ruffin@ki.se
Chiara Starvaggi Cucuzza, PhD student, chiara.starvaggi.cucuzza.2@ki.se
Susanne Sundqvist, research nurse, susanne.sundqvist@ki.se
Olafur Sveinsson, affiliated to research, olafur.sveinsson@ki.se
Emily Thorburn, research assistant, +46852482026, emily.thorburn@ki.se
Francesca Trogu, PhD student, francesca.trogu@ki.se
Suvi Virtanen, project coordinator, PhD student, +46852483217, suvi.virtanen@ki.se
Wanqing Wu, PhD student, wanqing.wu@ki.se
Selected publications
-
Article: NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION. 2023;10(1):e200056
-
Article: JAMA NEUROLOGY. 2022;79(11):1105-1112
-
Review: JOURNAL OF INTERNAL MEDICINE. 2021;289(6):771-791
-
Article: NEUROLOGY. 2021;96(11):e1574-e1584
-
Article: SCIENTIFIC REPORTS. 2021;11(1):1669
-
Editorial comment: NEUROLOGY. 2020;95(12):509-510
-
Article: NATURE COMMUNICATIONS. 2020;11(1):4071
-
Article: JAMA NEUROLOGY. 2020;77(8):974-981
-
Article: NEUROLOGY. 2020;94(11):e1201-e1212
-
Review: MULTIPLE SCLEROSIS JOURNAL. 2020;26(2):137-152
-
Article: JAMA NEUROLOGY. 2020;77(2):184-191
-
Article: NATURE COMMUNICATIONS. 2019;10(1):3081