Antisense oligonucleotides against Il6ra ameliorate cancer cachexia in mice.

Authors

Yuanyuan Wang, Qingtao Sun, Wenqiang Zheng, Lijie Han, Qian Zhang, Adrian R Krainer, Bo Li

Published in

Molecular therapy : the journal of the American Society of Gene Therapy. Aug 19, 2026. Epub Aug 19, 2026.

Abstract

Mounting evidence indicates that interleukin-6 (IL-6) plays an essential role in the development of cancer cachexia. Particularly, recent work showed that IL-6 drives cancer cachexia through neurons in the area postrema of the brainstem. However, there are currently no approved drugs for treating cancer cachexia. Here we developed a splice-switching antisense oligonucleotide (ASO)-based therapy for treating cancer cachexia by reducing IL-6 receptor (IL-6R) expression in the brain. In two mouse models of cancer cachexia, a single dose of ASOs, administered by intracerebroventricular injection after cancer onset, reduces IL-6R levels in the brainstem and ameliorates cachectic symptoms. It also extends survival in one of the models. In parallel, the ASO treatment reduces cancer-associated transcriptomic activation of inflammatory pathways in both the brainstem and skeletal muscle. We also developed ASOs that suppress human IL-6R expression, paving the road for clinical studies. Our study thus provides a new approach for treating cancer cachexia.

PMID:
42619263
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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