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Abstract Details

Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes
Multiple Sclerosis
MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)
132

To study the effect of FGFR tyrosine kinase inhibitors on oligodendrocytes in vitro.

Fibroblast growth factors (FGF) and their receptors (FGFR) are involved in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis (EAE), changes in FGF/FGFR as well as BDNF/TrkB signalling resulting from oligodendrocyte-specific deletion of FGFR1 and FGFR2, led to a less severe disease course and less myelin and axon degeneration. The FGFR tyrosine kinase inhibitors are used efficiently in experimental tumour models and patients with malignancies.
In the present study, tyrosine kinase inhibitors dovitinib and AZD4547 were applied to OLN-93 oligodendrocytes, the effects of FGFR inhibition were studied by immunofluorescence microscopy, protein and gene analyses.
FGFR inhibition decreased the proliferation of OLN-93 cells and resulted in reduced FGFR1, pERK and pAkt expression. Furthermore, it led to enhanced expression of BDNF and its receptor TrkB. The myelin proteins PLP and CNPase were upregulated by FGFR Inhibition.
These findings suggest that FGF/FGFR inhibition in oligodendrocytes enhance myelin expression. Inhibition of FGF/FGFR pathways may offer a therapeutic strategy for the treatment of multiple sclerosis.
Authors/Disclosures
Martin Berghoff, MD, FAAN (BundeswehrZentralkrankenhaus Koblenz)
PRESENTER 		Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MerckSerono. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb.
No disclosure on file
No disclosure on file
Vinothkumar Rajendran (Justus-Liebig University) Mr. Rajendran has nothing to disclose.
No disclosure on file
Srikanth Karnati No disclosure on file
Ranjithkumar Rajendran (Justus Liebig University) Mr. Rajendran has nothing to disclose.