Fredrik Piehl´s research group
Inflammation and neurodegeneration in the CNS diseases focusing on multiple sclerosis (MS)
Multiple sclerosis (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. Inflammation also occurs in purely mechanical injuries such as traumatic brain injury, which may contribute to worsening of the initial nerve damage. 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 purely preclinical project, in which the importance of genetic factors in experimental models of nerve injury and inflammation have been identified, the program now involves translational research in both experimental preclinical models and human diseases, where the main focus is on MS.
One of the most important clinical shortcomings of current MS treatment is that while we have gained access to increasingly effective disease modulatory drugs for the initial relapsing remitting phase of MS, treatment results in later, progressive stages remain disappointing.
Within the current project we have identified biomarkers for various disease processes that reflect what happens in the blood and brain tissue. We also use experimental models to understand in what molecular processes these biomarkers are involved in. Similarly, we use biomarkers to gain insights into mechanisms of action and to monitor treatment outcomes with our disease-modulating treatments. Uniquely in Sweden a drug not formally approved for MS (Mabthera/Rituxan) has become one of the most frequently used, in part through observational data provided by us. We will now start a large national follow-up program for people newly diagnosed with MS involving all Swedish university clinics and with funding from the US foundation Pcori. The study aims to generate information on safety and efficiency of MS treatments over longer time periods than is possible in traditional randomized trials and also to engage patients in the conduction of the study to a high extent.
A side project is to study if MabThera/Rituxan is superior to traditional treatment for patients newly diagnosed with myasthenia gravis (MG), an autoimmune disease of the nerves in which inflammation disrupts the signaling between nerves and muscles. The study Rinomax, which has received support from the Medical Research Council (clinical treatment research), randomize individuals with new-onset MG to either MabThera/Rituxan or placebo. Biomarker research is also conducted in MG to better understand underlying immunological disease processes.
- Genetic regulation of neurodegeneration and inflammation in experimental modeler for nerve damage.
- Identification of biomarkers in various disease stages of MS, in traumatic brain injury and psychiatric diseases.
- Clinical treatment research in MS and MG
MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction.
Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, et al
Nat. Genet. 2005 May;37(5):486-94
Strain influences on inflammatory pathway activation, cell infiltration and complement cascade after traumatic brain injury in the rat.
Al Nimer F, Lindblom R, Ström M, Guerreiro-Cacais AO, Parsa R, Aeinehband S, et al
Brain Behav. Immun. 2013 Jan;27(1):109-22
Naturally occurring variation in the Glutathione-S-Transferase 4 gene determines neurodegeneration after traumatic brain injury.
Al Nimer F, Ström M, Lindblom R, Aeinehband S, Bellander BM, Nyengaard JR, et al
Antioxid. Redox Signal. 2013 Mar;18(7):784-94
Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination.
Al Nimer F, Elliott C, Bergman J, Khademi M, Dring AM, Aeinehband S, et al
Neurol Neuroimmunol Neuroinflamm 2016 Feb;3(1):e191
Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.
Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, et al
Ann. Neurol. 2016 Jun;79(6):950-8
Faiez Al NimerAnknuten, Postdoc
Peter AlpingDoktorand, Forskarstuderande
Fredrik PiehlForskargruppsledare, Professor/överläkare