👤 Authors: Yuanyuan Wang, Qingtao Sun, Wenqiang Zheng, Lijie Han, Qian Zhang, Adrian R Krainer, Bo Li
Antisense oligonucleotides against Il6ra ameliorate cancer cachexia in mice.
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.
