EP0650597A4 - Diagnostisches verfahren zur bewertung der ätiologie des minderwuchse. - Google Patents
Diagnostisches verfahren zur bewertung der ätiologie des minderwuchse.Info
- Publication number
- EP0650597A4 EP0650597A4 EP93916678A EP93916678A EP0650597A4 EP 0650597 A4 EP0650597 A4 EP 0650597A4 EP 93916678 A EP93916678 A EP 93916678A EP 93916678 A EP93916678 A EP 93916678A EP 0650597 A4 EP0650597 A4 EP 0650597A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- growth hormone
- trp
- ghrp
- phe
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/61—Growth hormones [GH] (Somatotropin)
Definitions
- the present invention provides a method for diagnosing the etiology of short stature in children.
- Stimulated growth hormone GH secretion using a variety of provocative agents including 1-dopa, clonidine, arginine and insulin have been assessed in slowly or poorly growing children in an attempt to determine the etiology of short stature.
- provocative agents whose action is mediated by growth hormone releasing hormone (GHRH) cannot differentiate hypothalamic defects from pituitary defects in the GH neuroendocrine axis.
- GHRH growth hormone- releasing hormone
- patents 5,065,747 issued November 19, 1991, and 4,844,096 issued July 4, 1989 describe methods for reducing the variability in GH levels by administering somatostatin prior to provocative testing or prior to determining the etiology of growth hormone deficiency.
- the present invention provides a new and more effective way to use stimulated GH secretion as a reliable and effective tool for diagnosing GH secretory deficits in short- statured children.
- the present invention provides a diagnostic procedure for determining whether short stature in a child is due to a deficiency in growth hormone releasing hormone (GHRH) or GHRP-6 or a peptite which causes release of growth hormone (GH) by the same cellular mechanism.
- GHRH growth hormone releasing hormone
- GHRP-6 growth hormone releasing hormone
- the diagnostic procedure of the present invention is carried out by establishing baseline levels of growth hormone in the blood of the child having short stature, then administering sequentially a growth hormone releasing compound, GHRP-6, or a peptide which causes growth hormone release by the same cellular mechanism as GHRP-6, or the combination of GHRH and GHRP-6 and then measuring the changes, if any, in the levels of growth hormone in the blood of the short-statured child resulting from the three different administrations.
- GHRP-6 growth hormone releasing compound
- GHRH growth hormone releasing compound
- GHRP-6 a growth hormone releasing compound which causes growth hormone release by the same cellular mechanism as GHRP-6
- the growth hormone releasing compound can be administered either first or second, generally on different days, i.e., before or after the GHRP-6 or peptide which acts similarly at a cellular level.
- the quantities of each agent to be administered is any quantity known to be effective in causing an increase in growth hormone levels, i.e., an amount which will stimulate release of growth hormone.
- GHRH may not be the only endogenous agent that provides stimulation for GH secretion.
- a xenobiotic hexapeptide, GHRP-6 which has different binding characteristics from GHRH (E.E. Codd et al., Neuropharmacology 1989; ,28 . , 1139-1144 and A.D. Blake, et al., J. Endocrinol. 1991; 129. 11-19) and utilizes a different somatotroph second messenger system (K. Cheng et al., Endocrinol.
- GHRP-6 is effective in some, but not all, short-statured children to whom it is administered (C.Y. Bowers et al. , J. Clin. Endocrinol. Metab. 1991; 1 _, 292-298 and V.
- GHRP-6 is a hexapeptide having the following structure: His-D-Trp-Ala-Trp-D-Phe-Lys-NH 2 .
- GHRP-6 in practicing the present invention, GHRP-6, as well as all other synthetic peptides in the same class of drugs that release GH by the same cellular mechanism as GHRP-6 referred to hereinafter as GHRP-6 or analogs thereof, will be used as diagnostic agents in children for differential diagnosis of growth hormone (GH) deficiency of various etiologies.
- Responses to GHRP-6 or analogs thereof will be compared with those resulting from administration of the endogenous GH releasing hormone (GHRH) and from co-administration of GHRH and GHRP-6 to better understand the cause of growth deficits in short statured children.
- GHRH endogenous GH releasing hormone
- GHRP-6 acts as a functional analog for a yet undefined GHRH co- factor or co-secretagogue
- hyposensitivity to a provocative GHRH challenge could represent deficiency of that endogenous co-secretagogue (represented by GHRP-6) rather than down- regulation of pituitary receptor or deficits in GH synthesis and/or release.
- Such a child could have normal GHRH concentrations/secretion and a normal pituitary, but display poor GH secretion in the absence of the endogenous GHRP-6 analog.
- this child would respond normally to a challenge dose of GHRP-6 because his/her complement of GHRH would be available.
- the present invention provides a new clinical application for GHRP-6 and other synthetic GH secretagogues that function by the same mechanism as GHRP-6.
- the invention is important because it not only provides a reliable method for identifying children with low GH secretory capability, but also helps diagnose the etiology of GH deficiency and perhaps provide a key to appropriate treatment.
- children who are shorter than other children of a comparable age who have been identified as in need potentially of growth hormone or some agent that would stimulate growth hormone production would be monitored for the purpose of establishing a baseline level of growth hormone in the blood.
- the child is administered GHRH at a dose ranging from 100 ng/kg body weight to 100 mg/kg body weight.
- the GHRH peptide is administered and blood samples are monitored over a period of 120 minutes to determine whether the exogenous GHRH increased growth hormone levels.
- the child is administered GHRP-6 or an analog thereof at a dose of 100 ng/kg body weight to 1 mg/kg body weight for one day. Blood samples are measured for any change in growth hormone levels.
- Additional administration of peptides may be made but a day of rest, i.e., a day during which neither peptide type is administered should intervene administration days.
- the dosage amount can be varied to determine optimal dosages.
- the changes, if any, in growth hormone levels to either or both of GHRH or GHRP-6 or analog thereof will provide an insight to the etiology of the short stature condition of the child.
- any growth hormone releasing compound can be utilized in the diagnostic procedure of the present invention.
- GHRH is the preferred growth hormone releasing compound for use in the claimed invention.
- the growth hormone releasing compounds which may be used in practicing the present invention are any such compounds known to induce growth hormone (GH) secretion and include growth hormone releasing hormone (GHRH) (1-44) and analogs GHRH (1-40) and GHRH (1-29) thereof.
- GHRH growth hormone releasing hormone
- GHRH growth hormone releasing hormone
- GHRH growth hormone releasing hormone
- U.S. Patent 4,622,312 provides an excellent description of GHRH and analog thereof, which can be used in the presently claimed invention.
- Reissue patent RE33,699 provides a summary of patents which teach growth hormone releasing compounds.
- GHRP-6 and analogs thereof means GHRP-6 and any peptide compound that releases GH by the same cellular mechanism.
- the pentapeptide Tyr-D-Trp- Gly-Phe-Met-NH 2 (K. Cheng et al. , Endocrinol. 1989; 124. 2791-2798) is a useful analog in the release of GH.
- Other compounds considered analogs of GHRP-6 for purposes of the present invention have been reported. For example, C.Y.
- the growth hormone levels in the blood of the child can be measured by any well known procedures, e.g., using an immunoradiometric assay as described by C.Y. Bowers et al., J. Clin Endocrinol. Metab 1990; 7J), 975-982 or any other contemporary, scientifically accepted method.
- the appropriate replacement therapy can ensue whereby either a growth hormone releasing compound or a GHRP-6 or analog thereof or a combination of both GH secretagogues is administered to the child.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US90576092A | 1992-06-29 | 1992-06-29 | |
PCT/US1993/005955 WO1994000759A1 (en) | 1992-06-29 | 1993-06-22 | Diagnostic procedure for evaluating short stature etiology |
US905760 | 1997-08-04 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0650597A1 EP0650597A1 (de) | 1995-05-03 |
EP0650597A4 true EP0650597A4 (de) | 1996-12-18 |
Family
ID=25421421
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP93916678A Withdrawn EP0650597A4 (de) | 1992-06-29 | 1993-06-22 | Diagnostisches verfahren zur bewertung der ätiologie des minderwuchse. |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0650597A4 (de) |
CA (1) | CA2139326A1 (de) |
WO (1) | WO1994000759A1 (de) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5811074A (en) * | 1992-06-29 | 1998-09-22 | University Of South Florida | Method of diagnosing pituitary dependent growth hormone deficiency |
WO1996029002A1 (en) * | 1995-03-17 | 1996-09-26 | University Of South Florida | Method of diagnosing pituitary dependent growth hormone deficiency |
CU23016A1 (es) * | 2002-01-24 | 2005-01-25 | Ct Ingenieria Genetica Biotech | Método para la estimulación del crecimiento y resimétodo para la estimulación del crecimiento y resistencia a enfermedades en organismos acuáticos y fstencia a enfermedades en organismos acuáticos y formulación veterinaria ormulación veterinaria |
EP2547700A1 (de) * | 2010-03-17 | 2013-01-23 | Universität Regensburg | An das mia-protein (melanoma inhibitory activity) bindende peptide oder antikörper |
CN116459250A (zh) * | 2015-09-21 | 2023-07-21 | 卢莫斯制药公司 | 检测和治疗生长激素缺乏症 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622312A (en) * | 1984-09-24 | 1986-11-11 | Hoffmann-La Roche Inc. | Growth hormone releasing factor analogs |
US5246920A (en) * | 1992-06-15 | 1993-09-21 | University Of South Florida | Treatment of hyperprolactinemia |
-
1993
- 1993-06-22 WO PCT/US1993/005955 patent/WO1994000759A1/en not_active Application Discontinuation
- 1993-06-22 EP EP93916678A patent/EP0650597A4/de not_active Withdrawn
- 1993-06-22 CA CA 2139326 patent/CA2139326A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622312A (en) * | 1984-09-24 | 1986-11-11 | Hoffmann-La Roche Inc. | Growth hormone releasing factor analogs |
US5246920A (en) * | 1992-06-15 | 1993-09-21 | University Of South Florida | Treatment of hyperprolactinemia |
Non-Patent Citations (1)
Title |
---|
See also references of WO9400759A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP0650597A1 (de) | 1995-05-03 |
WO1994000759A1 (en) | 1994-01-06 |
CA2139326A1 (en) | 1994-01-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Chapman et al. | Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects | |
Corpas et al. | Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men | |
Ghigo et al. | New approach to the diagnosis of growth hormone deficiency in adults | |
Huhn et al. | Twenty-four-hour growth hormone (GH)-releasing peptide (GHRP) infusion enhances pulsatile GH secretion and specifically attenuates the response to a subsequent GHRP bolus. | |
Yuen et al. | American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency | |
Ghigo et al. | Enhancement of cholinergic tone by pyridostigmine promotes both basal and growth hormone (GH)-releasing hormone-induced GH secretion in children of short stature | |
CHIHARA et al. | Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity level in cerebrospinal fluid | |
Frystyk et al. | Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay | |
Ranke | Diagnosis of growth hormone deficiency and growth hormone stimulation tests | |
MIELL et al. | Effects of dexamethasone on growth hormone (GH)-releasing hormone, arginine-and dopaminergic stimulated GH secretion, and total plasma insulin-like growth factor-I concentrations in normal male volunteers | |
LIDDLE et al. | Regulation of pancreatic endocrine function by cholecystokinin: studies with MK-329, a nonpeptide cholecystokinin receptor antagonist | |
Alster et al. | The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly | |
Griffing et al. | Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension. | |
EP0650597A1 (de) | Diagnostisches verfahren zur bewertung der ätiologie des minderwuchse | |
Robertson et al. | Prolactin response to morphine in depression | |
Ghigo et al. | A new test for the diagnosis of growth hormone deficiency due to primary pituitary impairment: combined administration of pyridostigmine and growth hormone-releasing hormone | |
Ranke et al. | Testing with growth hormone-releasing factor (GRF (1–29) NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency | |
LOCHE et al. | Augmentation of growth hormone secretion in children with constitutional growth delay by short term clonidine administration: a pulse amplitude-modulated phenomenon | |
Facchinetti et al. | Neuroendocrine evaluation of central opiate activity in primary headache disorders | |
Ho et al. | Defining growth hormone deficiency in adults | |
Korbonits et al. | Hexarelin as a test of pituitary reserve in patients with pituitary disease | |
US5811074A (en) | Method of diagnosing pituitary dependent growth hormone deficiency | |
Popovic et al. | The effectiveness of arginine+ GHRH test compared with GHRH+ GHRP‐6 test in diagnosing growth hormone deficiency in adults | |
Pozo et al. | Growth hormone secretion in children with normal variants of short stature | |
Korbonits et al. | Diagnosis of growth hormone deficiency in adults |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19950123 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 19961105 |
|
AK | Designated contracting states |
Kind code of ref document: A4 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Withdrawal date: 19970113 |