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Unidentified

ABSTRACT: Identification of Effective Mechanism of IBD Therapeutic Probiotics via Genome and Metagenomic Analysis (KAP230536)

PROVIDER: PRJDB19444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR675861_1.fastq.gz	Fastqsanger.gz
	DRR675861_2.fastq.gz	Fastqsanger.gz
	DRR675862_1.fastq.gz	Fastqsanger.gz
	DRR675862_2.fastq.gz	Fastqsanger.gz
	DRR675863_1.fastq.gz	Fastqsanger.gz

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Therapeutic IL-6 trans-signalling inhibition by olamkicept (sgp130Fc) in patients with active inflammatory bowel disease

Project description:Background A large unmet therapeutic need exists in inflammatory bowel diseases (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL-6/IL-6R blockade is limited by profound immunosuppression. Evidence has emerged, that chronic pro-inflammatory activity of IL-6 is mainly mediated by trans-signalling via a complex of IL-6 bound to soluble IL-6R engaging the gp130 receptor without the need of membrane bound IL6R. We have developed a decoy protein, sgp130Fc, which exclusively blocks IL-6 pro-inflammatory trans-signalling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression. Methods We present a 12-week, open label, prospective phase IIa trial (FUTURE) in 16 patients with active IBD treated with the trans-signalling inhibitor olamkicept (sgp130Fc) to assess molecular mechanisms, safety and effectiveness of IL-6 trans-signalling blockade in vivo. We performed in-depth molecular profiling at various time points before and after therapy induction to identify the mechanism of action of olamkicept. Results Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-TNF (infliximab) or anti-integrin (vedolizumab) therapies was identified. Conclusion Our data suggest that blockade of IL-6 trans-signaling holds large promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy of IBD.

2021-04-10 | GSE171770 | GEO

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Project description:Investigation of health functionalities of kimchi probiotics in vivo (KAP220299)

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