Degenerative mechanisms and treatment optimization in neuroinflammatory disorders of the central nervous system

Demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), are associated with irreversible neuronal and myelin lesions. The overarching goal of our laboratory is to optimize the clinical management of these incurable diseases. In the motor and the visual systems, neuronal and myelin damage are responsible for important functional deficits. Current treatments are based on the administration of anti-inflammatory and immunosuppressive drugs, the efficacy of which depends on the efficient detection and monitoring of disease activity. New sensitive and non-invasive clinical approaches are required to identify early signs of attacks, as delayed or inappropriate treatments can contribute to neurological deteriorations. In addition, the availability of regenerative treatments, i.e. therapies able to stimulate neuronal and myelin repair, is a major unmet clinical need. Regenerative treatment may counteract disease progression and prevent permanent disabilities.

The general objectives of our team are to find new methods to diagnose MS and NMOSD, to monitor their evolution and to repair injured neurons. Consequently, using state-of-the art techniques, the CHAN/PERNET laboratory has developed the following translational projects in the brain, spinal cord and visual system:

  1. The search of new blood biomarkers for NMOSD and MS patients. Here, the secretion of glial and neuronal-derived proteins is examined in the blood of patients by proteomic analysis in active and stable disease phases. Inflammation and autoantibodies may specifically induce the release of CNS proteins that may serve as biomarkers reflecting disease activity. This project involves Mrs. Victoria Lim Falk, Ph. D. student in our group, and is realized in collaboration with CSL Behring and Prof. Smita Saxena (Dept of Neurology, Bern University Hospital-Inselspital and DBMR). The results of this project may allow to improve the detection of disease activity in MS and NMOSD.
  2. The use of the intranasal pathway for the delivery of regenerative antibodies in experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. The goal of this EU-funded study, that is part of the Bio2Brain project and involves Mr. Sebastian Spiegel, PhD student in our group, is to test the intranasal pathway of administration for the neutralization of CNS antigens contributing to the pathogenesis of MS and cognate diseases with monoclonal antibodies. The results of this study may be used to design a new administration method capable of bypassing the blood-brain barrier, that represents a major obstacle to the passage of intravenously-injected antibodies. Presently, our data show that the intranasal pathway is effective in mitigating the motor deficits and myelin lesions of EAE with an anti-Nogo-A antibody called 11C7.
  3. The influence of the visual system on the visual and non-visual symptoms of EAE. In this study, the consequences of EAE-induced visual defects on non-visual symptoms (e.g. spinal cord demyelination) and systemic inflammatory response are investigated. The environment, including light stimulation, is thought to exert a strong influence on MS relapse and severity. By modulating retinal activity, the course of EAE is followed in the spinal cord and in the brain. This project is carried out by our postdoctoral fellow, Dr. Julius Baya Mdzomba, in collaboration with Dr. Sandrine Joly from the department of Ophthalmology of Bern University Hospital-Inselspital.
  4. The characterization of B cell-dependent EAE in the degeneration of neuronal and glial cells of the visual and the motor system. A B cell-dependent EAE model that has been developed by our collaborator, Prof. Luc Vallières, at the University Laval in Quebec City, Canada, is currently used as an improved animal model for analyzing the mechanisms of MS and NMOSD. This project is done by Mrs. Auste Asadauskas, (M.Sc. medical student), Dr. Mdzomba and Dr. Joly. The results of this study are expected to show differences between this model and the classical EAE model that does not require B cells. Ultimately, it may be used to test new therapeutic strategies.