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Antisense Therapeutics Ltd, Level 1, 10 Wallace Ave, Toorak, Victoria 3142, Australia
¹ Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
² Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia

(Requests for offprints should be addressed to G Tachas; Email: george.tachas{at}antisense.com.au)

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.

This article has been cited by other articles:

				M. J. Waters and J. L. Barclay Does Growth Hormone Drive Breast and Other Cancers? Endocrinology, October 1, 2007; 148(10): 4533 - 4535. [Full Text] [PDF]