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

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

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

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

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

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

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

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

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

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

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

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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.

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