scholarly journals A long-acting GH receptor antagonist through fusion to GH binding protein

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ian R. Wilkinson ◽  
Sarbendra L. Pradhananga ◽  
Rowena Speak ◽  
Peter J. Artymiuk ◽  
Jon R. Sayers ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Binding Protein ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Long Acting

scholarly journals Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

2000 ◽  
Vol 167 (2) ◽  
pp. 295-303 ◽  
Author(s):  
JW van Neck ◽  
NF Dits ◽  
V Cingel ◽  
IA Hoppenbrouwers ◽  
SL Drop ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Gh Receptor ◽  
Igf I ◽  
Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

Growth Hormone Receptor Antagonist Therapy in Acromegalic Patients Resistant to Somatostatin Analogs*

2000 ◽  
Vol 85 (8) ◽  
pp. 2958-2961 ◽  
Author(s):  
Vivien S. Herman-Bonert ◽  
Kenneth Zib ◽  
John A. Scarlett ◽  
Shlomo Melmed
Keyword(s):  
Growth Hormone ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Growth Hormone Secretion ◽  
Primary Therapy ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Octreotide Therapy

Transsphenoidal surgical resection is the primary therapy for acromegaly caused by GH secreting pituitary adenomas. Medical therapy for patients not controlled by surgery includes primarily somatostatin analogs and secondarily dopamine agonists, both of which inhibit pituitary growth hormone secretion. A novel GH receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits peripheral insulin-like growth factor-1 generation. Six patients resistant to maximal doses of octreotide therapy received pegvisomant—three received placebo or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and pegvisomant 10–20 mg/d for 12 weeks. Thereafter, all patients received daily pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total IGF-1 levels were normalized in all six acromegalic patients previously shown to be resistant to somatostatin analogs via a novel mechanism of peripheral GH receptor antagonism. The GH receptor antagonist is a useful treatment for patients harboring GH-secreting tumors who are resistant to octreotide.

Impact of the GH-receptor antagonist pegvisomant on mammographic breast density in postmenopausal acromegalic women

2016 ◽  
Author(s):  
Ammar Muhammad ◽  
Gianluca Ficarra ◽  
Sanne Franck ◽  
Elena Nazarri ◽  
Alberto Tagliafico ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Breast Density ◽  
Mammographic Breast Density ◽  
Gh Receptor ◽  
Gh Receptor Antagonist

scholarly journals Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study

2007 ◽  
Vol 156 (1) ◽  
pp. 75-82 ◽  
Author(s):  
I Schreiber ◽  
M Buchfelder ◽  
M Droste ◽  
K Forssmann ◽  
K Mann ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Receptor Antagonist ◽  
Signs And Symptoms ◽  
Efficacy Evaluation ◽  
Safety And Efficacy ◽  
Gh Receptor ◽  
Elevated Liver Enzymes ◽  
Igf I ◽  
Gh Receptor Antagonist

Objective: The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice. Design: GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection. Methods: Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement. Results: IGF-I levels decreased from 1.75±0.91-fold the upper limit of normal at baseline to 1.05± 0.62 at the 6-month visit, 0.96±0.60 at the 12-month visit, and to 0.89±0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy was 51.8±35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4±45.9 to 101.5± 42.8 mg/dl after 6 months (P<0.01) and to 100.6±33.2 mg/ml after 12 months (P<0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in >1% were injection site reactions in 7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. Conclusions: Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.

scholarly journals Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant

2006 ◽  
Vol 154 (6) ◽  
pp. 805-806 ◽  
Author(s):  
J Feenstra ◽  
M O van Aken ◽  
W W de Herder ◽  
R A Feelders ◽  
A J van der Lely
Keyword(s):  
Adverse Drug Reaction ◽  
Combined Treatment ◽  
Somatostatin Analog ◽  
Acromegalic Patient ◽  
Hepatic Enzyme ◽  
Hepatic Enzymes ◽  
Drug Induced ◽  
Gh Receptor ◽  
Gh Receptor Antagonist ◽  
Long Acting

We report on a patient with acromegaly who developed severe drug-induced hepatitis during combined treatment with the long-acting somatostatin-analog octreotide and the GH receptor antagonist pegvisomant. The hepatic enzyme disturbances normalized after discontinuation of pegvisomant. After rechallenge with monotherapy pegvisomant, however, the hepatic enzyme disturbances reappeared within a few weeks, indicating that most likely pegvisomant alone and not the long-acting somatostatin analog or the combination of these two drugs was responsible for this case of drug-induced hepatitis. Clinicians should be aware of this potential severe adverse drug reaction and therefore frequent control of hepatic enzymes is mandatory during treatment with pegvisomant.

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