Activin receptor ligand traps in chronic kidney disease

Current Opinion in Nephrology and Hypertension
Wolfgang Jelkmann

Abstract

Sotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias, including renal anemia. The mechanism of the action of the novel drugs is incompletely understood, but it seems to be based on the inactivation of soluble proteins of the transforming growth factor-ß (TGFß) family. This review considers pros and cons of the clinical use of the drugs in reference to the current therapy with recombinant erythropoiesis-stimulating agents (ESAs). One or more activin type-II receptor (ActRII) ligands appear to inhibit erythroid precursors, for example growth and differentiation factor 11. Trapping of these ligands by the recombinant ActRII fusion proteins, sotatercept and luspatercept increases red blood cell numbers and hemoglobin levels in humans. Reportedly, the novel compounds were well tolerated in trials on healthy volunteers and patients suffering from anemia due to chronic kidney disease or malignancies. On approval, the drugs may prove particularly useful in patients suffering from ineffective erythropoiesis, such as in myelodysplastic syndrome, multiple myeloma or ß-thalassemia, where ESAs are of little use. I...Continue Reading

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Citations

Jun 26, 2018·Current Opinion in Nephrology and Hypertension·Sehrish AliSankar D Navaneethan
Nov 7, 2019·Journal of Clinical Medicine·Małgorzata BanaszkiewiczKatarzyna Krzanowska
Mar 7, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Yuxia WangWang Jidong
Nov 13, 2019·Current Opinion in Nephrology and Hypertension·Neel Mehta, Joan C Krepinsky
Jun 20, 2020·Blood·Jeffrey A Gilreath, George M Rodgers
Sep 18, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Giuseppe CiancioloMario Cozzolino
Feb 27, 2020·Scientific Reports·Yi-Lin TsaiShing-Jong Lin
Jan 26, 2020·International Journal of Molecular Sciences·Anna Gluba-BrzózkaJacek Rysz
Oct 17, 2019·Nutrients·Sajidah Begum, Gladys O Latunde-Dada

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