Abstract Details

Title microRNA as a Therapeutic Target in Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) S50 - (-)

Poster/Presentation
Number 004

Objective

Background MicroRNAs (miRNA) act as a regulators of the immune system. We have already demonstrated a significant changes of miR-301a during the development of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis (MS). miR-301a has been implicated in the process of the T helper cell (Th) differentiation and development of the proautoimmune Th17 subtype. Here, we are validating its role as therapeutic target by in vivo miR-301 manipulation and assessment of EAE susceptibility.

Design/Methods To in vivo manipulate the miR-301a activity a set of specific oligonucleotide mimics and antagomir inhibitors was used. Active myelin antigen immunization EAE model and myelin specific Th transfer model have been assessed. To validate the impact of the in vivo manipulation of miR-301a on EAE a fraction of CNS infiltrating lymphocytes have been isolated and analyzed. Clinical course and CNS pathology was also assessed.

Results The specific manipulation of miR-301a with inhibitors and mimics revealed that miR-301a contributed to the development of the Th17 via targeting of the Protein Inhibitor of Activated STAT3. Mice that received Th expressing a mimic of miR-301a developed a very aggressive form of EAE that resulted in the death of all animals. In contrast, the group that received Th with an antagomir for miR-301a developed a very mild EAE. miR-301a inhibition during EAE have been correlated with decreased in vivo Th infiltration in the CNS as well as diminished ability to secrete IL-17. These findings have been corroborated by the results of the systemic administration of specific miR-301a inhibitor during actively induced EAE, that demonstrated a significant attenuation of EAE.

Conclusions Our findings confirm the role of miR-301a in the in vivo development of Th17 cells. miR-301a inhibition strategies represent a promising therapeutic option for autoimmune demyelination.

Authors/Disclosures
Marcin P. Mycko, MD (Medical University of Lodz, Department of Neurology) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Beata Sliwinska	No disclosure on file
	No disclosure on file
Krzysztof W. Selmaj (University of Warmia and Mazury)	Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.

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