Biomarkers for the efficacy of somatostatin analogue treatment

A growth-stimulating hormone and biomarker technology, applied in the field of gene expression profiling for growth regulation, can solve the problems of insufficient growth control and contraindication of surgical operations

Inactive Publication Date: 2007-01-31
NOVARTIS AG
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  • Abstract
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  • Claims
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AI Technical Summary

Problems solved by technology

[0003] Clinically useful somatostatin analog Sandostatin (Sandostatin  ) and somatolin for the treatment of patients with acromegaly for whom surgery does not adequately control growth and insulin-like growth factor I (IGF-I) levels or where surgery is contraindicated

Method used

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  • Biomarkers for the efficacy of somatostatin analogue treatment

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Embodiment

[0038] Gene expression profiles in pasireotide-induced monkeys

[0039] Foreword and Summary

[0040] Microchip gene expression analysis was performed using monkey tissues treated with subtherapeutic doses of pasireotide for 14 days. The results of these assays were analyzed to identify the mode of action of pasireotide relevant for therapeutic applications.

[0041] All monkey tissues examined (thyroid, brown fat, pituitary, pancreas, liver, kidney, spleen) demonstrated the association of natural somatostatin 14 (SST-14) and somatostatin 28 (SST-28) with growth-promoting Changes in genes regulated by statin receptor (SSTR) binding. The transcriptional profile reflects the known effects of somatostatin on growth hormone / insulin-like growth factor 1 (GH / IGF-1), the glucagon / insulin axis, and on cell proliferation. However, the compounds significantly affected the transcriptional levels of other related genes such as insulin-like growth factor 2 (IGF-2) in the pituitary and k...

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Abstract

Gene expression analysis was performed on monkey tissues treated with subtherapeutic doses of the somatostatin analog pasireotide for 14 days. The assay results were performed in order to identify the mode of action of pasireotide relevant for therapeutic applications. Effects on the growth hormone / IGF-1 and glucagon / insulin axes were reflected in changes in transcript levels in several organs. The expressed genes can be used as surrogate markers of pasireotide biological activity, especially IGF-2 is found in the pituitary gland and kidney.

Description

field of invention [0001] The present invention relates generally to in vitro assays of tissue samples, and more particularly to aspects of gene expression profiling with respect to growth regulation. Background of the invention [0002] Somatostatin (SST-14; SRIF) is a cyclic tetradecapeptide hypothalamic hormone containing a disulfide bond between positions 3 and 14. See US Patent No. 6,225,284, incorporated herein by reference. Somatostatin also exists as a 28 amino acid peptide (SST-28). In its mechanism of action, somatostatin inhibits the release of growth hormone (GH) and thyrotropin (TSH), thereby inhibiting the release of insulin and glucagon and reducing gastric secretion. Metabolism of somatostatin by aminopeptidases and carboxypeptidases results in a short duration of action of somatostatin. Somatostatin binds to five different high affinity membrane-associated receptor (SSTR) subtypes with relatively high affinity for each subtype. Growth hormone and thyrotr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/31A61P35/00C12Q1/68
CPCC12Q1/6883A61K38/31C12Q2600/158C12Q2600/106C12Q2600/136A61P35/00
Inventor M·索尼耶
Owner NOVARTIS AG
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