Abstract Details

Title Peg-Interferon beta 1a induces a sustained and long lasting overexpression of interferon related genes.

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-073

Objective

Evaluation of biological activity of Pegylated (PEG)-IFNb 1a compared to IFNb 1a in Multiple Sclerosis patients.

Background Pegylation of IFNb improves its pharmacokinetic and pharmacodynamic profiles, increases the molecular half-life and maintains the efficacy. While clinical effects of PEG-IFNb have been widely investigated, evidences about the sustained biological activity of the drug are lacking.

Design/Methods Eight patients treated with IFNb 1a (single weekly intra-muscolar injection) and 9 patients treated with PEG-IFNb 1a (sub-cutaneous injection every two weeks) were enrolled. Whole transcriptome sequencing was performed on peripheral blood mononuclear cells collected at different time points: before treatment injection (T0) and at 3, 24 hours and 4, 7, 8, 11, 14 days after the injection (including additional injection at day 7 for IFNb 1a). Differential expression analysis was done with EdgeR Bioconductor package (ANOVA-like) using as reference T0 for each drug. The functional class enrichment of the genes was investigated using EnrichR (http://amp.pharm.mssm.edu/Enrichr/).

Results 250 differentially expressed genes were detected in PEG-IFNb treated samples compared to T0, 201 of them are in common with those differentially expressed in IFNb (311). Interferon receptor expression was not affected during the time course. The kinetics of interferon response was different between the two drugs. PEG-IFNb induced, as IFNb, an increase in genes expression at 3 and 24 hours after injection. However, the intensity of interferon responsive genes remained higher compared to that observed for IFNb. Specifically, upon PEG-IFNb treatment, 13 type I interferon related genes were still overexpressed compared to T0 even after 11 days from the injection. This response was exhausted after 4 days in IFNb 1a.

Conclusions PEG-IFNb elicits a long lasting interferon response which leads to an overexpression of interferon related genes till 11 days after injection. Data from this study provides a useful basis to set up an assay for the monitoring of biological activity of PEG-IFNb.

Authors/Disclosures
Antonio Bertolotto, MD, FAAN (Ospedale Koelliker) PRESENTER	Dr. Bertolotto has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Simona Malucchi	No disclosure on file
	No disclosure on file

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