News

M. Sospedra and Team, Science Translational Medicine 10.10.2018

In the journal Science Translational Medicine, the scientists report that T cells – i.e. the immune cells responsible for pathological processes – react to a protein called GDP-L-fucose synthase. This enzyme is formed in human cells as well as in bacteria frequently found in the gastrointestinal flora of patients suffering from multiple sclerosis. “We believe that the immune cells are activated in the intestine and then migrate to the brain, where they cause an inflammatory cascade when they come across the human variant of their target antigen,” says Mireia Sospedra.

For the genetically defined subgroup of MS patients examined by the researchers, results show that gut microbiota could play a far greater role in the pathogenesis of the disease than previously assumed. Mireia Sospedra hopes that these findings can soon also be translated into therapy; she plans to test the immunoactive components of GDP-L-fucose synthase using an approach that the researchers have been pursuing for several years already.

Re-educating the immune system

“Our clinical approach specifically targets the pathological autoreactive immune cells,” says Sospedra. This approach therefore differs radically from other treatments that are currently available, which throttle the whole immune system. While these treatments often succeed in stopping the progression of the disease, they also weaken the immune system – and can thus cause severe side effects.

The clinical approach of the research group involves drawing blood from MS patients in a clinical trial and then attaching the immunoactive protein fragments onto the surface of red blood cells in a laboratory. When the blood is reintroduced into the bloodstream of patients, the fragments help to “re-educate” their immune system and make it “tolerate” its own brain tissue. This therapeutic approach aims for effective targeted treatment without severe side effects.

Link to paper

 

Roland Martin and team - Cell Publication 30.08.2018

The investigations of the scientists Dr. Ivan Jelcic and Dr. Faiez Al Nimer under the lead of Prof. Martin and Dr. Sospedra at the USZ / UZH and in cooperation with the team of Prof. Olsson and Prof. Piehl at the Karolinska Institute have led to groundbreaking new findings on the disease mechanisms of MS.

Based on an experimental human in vitro system, an increased activation and cell division of autoreactive T cells from the peripheral blood of MS patients could be identified. Interestingly, the research team showed that this increased activation is mainly dependent on the interaction of autoreactive T cells with B cells.

The elimination of B cells, e.g. with therapy-used antibodies that deplete B cells, effectively inhibits T cell activation. So far, this mechanism was unknown. Another novelty of the work is the finding that dividing, autoreactive T cells in the blood are especially those that are also found in the brain lesions of MS patients. This indicates that activation of the autoreactive T cells by B cells in the peripheral blood leads to the activation of T cells in the brain and inflammatory lesions.

The research team has thus decoded a decisive step in the development of MS with these new research results on the interaction between B and T cells. The latter not only explains the previously unclear mechanism of action of therapeutically efficient B-cell depletion in MS, but also paves the way for new therapeutic approaches and research on the foundations of MS.

Open Access Cell Publication:

Jelcic, I., and Al Nimer, F. et al. Cell (2018)

https://doi.org/10.1016/j.cell.2018.08.011

SRF Puls "Radikale MS-Thrapie - Wie weiter?"

12.02.2018

Special Broadcast of the Schweizer Rundfunk about "Autologous hematopoietic stem cell transplanation (aHSCT) in Multiple Sclersosis" with Roland Martin as expert. (in German). This Broadcast is a follow-up Broadcast to the one released a year ago (20.02.2017)

Puls SRF Sendung zum Thema "Autologe hämatopoetische Stammzelltransplantation (aHSCT) in Multiple Scleros" mit Roland Martin als Experte (auf Deutsch).

https://www.srf.ch/sendungen/puls/radikale-ms-therapie-wie-weiter

 

SRF Puls "MS Stammzelltherapie"

20.02.2017

Special Broadcast of the Schweizer Rundfunk about "Autologous hematopoietic stem cell transplanation (aHSCT) in Multiple Sclersosis" with Roland Martin as expert. (in German)

Puls SRF Sendung zum Thema "Autologe hämatopoetische Stammzelltransplantation (aHSCT) in Multiple Scleros" mit Roland Martin als Experte (auf Deutsch).

https://www.srf.ch/sendungen/puls/ms-stammzelltherapie-zwischen-skepsis-und-letzter-hoffnung

Pfizer Price for Dr. Ivan Jelčić

We congratulate Dr. Ivan Jelčić for receiving the Pfizer price 2017 in Immunology together with Dr. Benoît Combaluzier, Neurimmune AG.

Dr. Jelčić and Dr. Combaluzier found that patients developing a PML had an inefficient antibody recognition of these PML-associated JC-polyomavirus variants. However, certain patients recovering from the PML and eliminating the JC virus from the brain form a broad spectrum of antibodies to these variants of the JC polyoma virus.

The researchers have succeeded in replicating specific human monoclonal antibodies from these patients, which have a neutralizing effect and can recognize the variants of this PML-associated JC-polyomavirus. The discovery of these antibodies is a breakthrough finding in the development of a possible therapy for this severe viral brain infection and also provide important insights into the human immune response to JC-polyomavirus.

http://www.pfizerforschungspreis.ch/de/preistr%C3%A4gerinnen#ivan

http://www.news.uzh.ch/de/articles/2017/pfizer-forschungspreis.html

New publications

Gaede, G., Tiede, M., Lorenz, I., Brandt, A.U., Pfueller, C., Dörr, J., Bellmann-Strobl, J., Piper, S.K., Roth, Y., Zangen, A., Schippling, S., Paul, F.  Safety and preliminary efficacy of deep transcranial magnetic stimulation in MS-related fatigue. Neurol Neuroimmunol Neuroinflamm. (2018) 5,e423.
Manogaran⁠a⁠, P., Walker-Egger⁠, C., Samardzija⁠c, M., Waschkies⁠, C., Grimm⁠, C., Rudin⁠, M., Schippling⁠, S. Exploring experimental autoimmune optic neuritis using multimodal Imaging. NeuroImage. (2018), in press.
Oberwahrenbrock, T., Traber, G. L., Lukas, S., Gabilondo, I., Nolan, R., Songster, C., Balk, L., Petzold, A., Paul, F., Villoslada, P., Brandt, A. U., Green, A. J., Schippling, S. Multicenter reliability of semiautomatic retinal layer segmentation using OCT. Neurol Neuroimmunol Neuroinflamm. (2018), 5:e449.

Find all publications related to the CRPPMS under the section "publications"
 

New Articles

Article in UZH Magazin

published 12th of December 2016 (in German)

Neustart des Immunsystems (PDF, 14835 KB)

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