| abstract |
Human growth hormone (GH) variant that has GH antagonistic activity and that comprises the following amino acid substitutions: H18D, H21N, G120K, R167N, K168A, D171S, K172R, E174S, I179T compared to the amino acid sequence of GH native shown in SEQ ID NO: 2, and oligonucleotide 15 to 30 nucleobases in length comprising at least one modified internucleoside junction, sugar moiety or nucleobase, directed to a nucleic acid encoding human growth hormone receptor (GHR) for inhibiting GHR expression, for use in a method for the treatment or prevention of disease caused by and / or associated with an increased level of insulin-like growth factor I (IGF-I), wherein the disease is acromegaly, diabetic retinopathy, diabetic nephropathy, or an IGF-I positive cancer such as prostate, myeloma, lung, breast, or colon cancer, the method comprising administering to a subject in need of the GH variant in combination with the oligonucleotide, thereby reducing the level of IGF-I in the subject. |