Immuno-Therapy and Diagnosis of Nervous System Diseases

PI:       
Dr. M. Losen

Collaborators:   
Prof. M. De Baets
Prof. W. Buurman
Dr. P. Martinez
Dr. P. Molenaar

Postdocs:   
Dr. I. Koneczny
Dr. A. Saxena

PhD-students:   
M. Mané-Damas MSc.
J. Stevens MSc.

Focus of research:   
We are using animal and cell culture models of Alzheimer’s disease (AD) and myasthenia gravis (MG) to develop new diagnostic methods, investigate disease mechanisms and treatment strategies

In a familial AD model, we are investigating the efficacy and side effects of anti-inflammatory and pro-inflammatory antibodies against amyloid beta (Aβ).
This research line is supported by a Hersenstichting fellowship.

In collaboration with Prof.dr. Guus van Dongen (VUMC) and with support from the Internationale Stichting Alzheimer Onderzoek, we are developing a positron emission tomography (PET) imaging method using zirconium-labelled antibodies in the central nervous system. For this immuno-PET research, we are currently investigating the diagnostic value of specific antibodies against different conformational forms of Aβ.

In MG, we are investigating the possible use of proteasome inhibitors for targeting autoimmune plasma cells. Long-living plasma cells are resistant against broad-range immunosuppressants and are therefore a major problem in the current treatment of MG and other antibody-mediated autoimmune diseases. Plasma cells depend on their proteasome to sustain high-rate protein synthesis. Consequently, proteasome inhibitors have the capacity to kill plasma cells by inducing the terminal unfolded protein response.

With support from the Princess Beatrix Fonds and The Netherlands Organisation for Health Research and Development, we are investigating disease pathology in a rare form of MG with muscle-specific kinase antibodies. For this purpose, we are generating monoclonal autoimmune B-cells from these patients. The cell lines are used to define fine antigen-specificities of individual patients’ antibodies and to develop an animal model that can be used for testing future therapies.