Abstract
Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2'-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.
Citations
Feb 7, 2008·Journal of Mammary Gland Biology and Neoplasia·Jo K PerryPeter E Lobie
May 16, 2009·Advances in Therapy·Sampath Satish KumarRobert D Murray
Aug 2, 2012·The Journal of Clinical Investigation·Emmanuel SommMichel L Aubert
Aug 28, 2007·International Journal of Nanomedicine·Ferdinand RoelfsemaJohannes Romijn
Apr 15, 2008·Expert Opinion on Biological Therapy·Ferdinand RoelfsemaJohannes A Romijn
Jun 10, 2008·Expert Opinion on Emerging Drugs·Philippe Chanson
Jan 10, 2014·Expert Opinion on Emerging Drugs·Sylvère Störmann, Jochen Schopohl
Nov 28, 2015·Nature Reviews. Endocrinology·Shlomo Melmed
Jul 3, 2015·EBioMedicine·Ferdinand Roelfsema
Apr 16, 2016·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Steve Harvey, Carlos G Martinez-Moreno
Mar 17, 2007·Retrovirology·Nicolas GilletLuc Willems
Jan 26, 2008·Hormone Research·A M Lichanska, M J Waters
Jun 29, 2016·Expert Opinion on Pharmacotherapy·Filippo MaffezzoniAndrea Giustina
Oct 18, 2016·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·F MaffezzoniA Giustina
May 24, 2018·European Journal of Endocrinology·Peter J TrainerMartin Bidlingmaier
Sep 19, 2007·Endocrinology·Michael J Waters, Johanna L Barclay
Sep 14, 2013·Endocrinology·Emmanuel SommMichel L Aubert
Sep 18, 2020·Expert Opinion on Emerging Drugs·Claudia CampanaFederico Gatto
Jul 1, 2016·Expert Review of Endocrinology & Metabolism·Katharina Schilbach, Jochen Schopohl
Feb 19, 2019·Signal Transduction and Targeted Therapy·Man LuJo K Perry