DeCure for Isolated growth hormone deficiency type IB
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for isolated growth hormone deficiency type IB — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIsolated growth hormone deficiency type IB maps to a 4-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for isolated growth hormone deficiency type ib is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
growth hormone releasing hormone receptor (GHRHR) — GHRHR is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet plmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7CZ5 · 2.6 Å · ligand PALMITIC ACID (PLM). Experimental structure, not a prediction.
What the evidence adds up to
In a 2001 study, 18 prepubertal children with idiopathic growth hormone deficiency received oral ibutamoren mesylate (MK-0677), a nonpeptide growth hormone secretagogue, for 7 to 8 days. At the higher dose of 0.8 mg/kg per day, median increases from baseline were 3.8 microg/L for serum GH peak concentration, 4.3 microg x h/L for GH area under the curve, 12 microg/L for serum IGF-I, and 0.4 microg/L for IGFBP-3. No changes were seen in prolactin, glucose, cortisol, or insulin. The authors concluded that short-term ibutamoren can increase GH and IGF-I in some children with GH deficiency, but no data on growth velocity or long-term outcomes were provided.
Daily injections of recombinant human growth hormone have been available since 1985 and are considered safe and effective for short stature in children and adult GH deficiency. A 2019 review notes that long-acting formulations using depot, PEGylated, pro-drug, albumin-binding, or fusion protein technologies are under development, with two products on the market in China and South Korea. A 2018 review of the first approved biosimilar rhGH confirms its equivalence to the original product in clinical trials and real-world studies, with the PATRO study ongoing to assess long-term efficacy and safety.
A 2006 study compared standard-dose GH treatment (0.5 IU/kg/week) in 140 non-GHD short children with 246 untreated short children. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group for both sexes. When subgroups matched for height SDS at baseline were compared, there were no significant differences in adult height, adult height SDS, or height SDS change. The authors concluded that ordinary GH treatment at the fixed Japanese dose of 0.175 mg/kg/week does not improve adult height in non-GHD short children.
What is still missing is a randomised controlled trial of ibutamoren mesylate with growth velocity or adult height as the primary endpoint in isolated GH deficiency type IB. The 2001 study was only 7–8 days long and did not measure growth. For biosimilar rhGH, final results from the PATRO post-authorisation study are pending. No long-acting GH formulation has been approved in Europe or the United States for this specific indication. Patient stratification by genetic subtype and baseline IGF-I levels has not been tested in any of these studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone–insulin‐like growth factor I axis in growth hormone–deficient children
AbstractIbutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH) secretagogue, stimulates GH release through a pituitary and hypothalamic receptor that is different from the GH-releasing hormone receptor. We evaluated the safety and tolerability and the GH-insulin-like growth factor (IGF) responses to two dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to 8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height < 10th percentile for age, and a maximum GH response of < or = 10 microg/L to two different GH stimulation tests. The children were assigned as follows to one of three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day 15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in groups I and II were studied first to assess safety at the low dose before advancement to the high dose. Hormonal profiles were evaluated on day -1 (baseline) and day 15, and the results were expressed as the change from baseline within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8 days (group III), the median increases (on day 15) from baseline were as follows: 3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3 microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to 116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum cortisol, and insulin concentrations or 24-hour urinary free cortisol after administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We conclude that short-term administration of ibutamoren mesylate can increase GH, IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound is applicable for testing its effect on growth velocity.
Archives of Endocrinology and Metabolism · 2019 · 30 citations · open access
Perspectives on long-acting growth hormone therapy in children and adults
AbstractGrowth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.
Anales de Pediatría (English Edition) · 2018 · 2 citations · open access
Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice
AbstractIntroduction Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. Materials and methods This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. Results The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. Conclusion The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug.
No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment
AbstractIt is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below -2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.
Perspectives on long-acting growth hormone therapy in children and adults
AbstractABSTRACT Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7
Клінічна ендокринологія та ендокринна хірургія · 2011 · 0 citations
Діагностика та лікування соматотропної недостатності у дітей
AbstractThe article presents criteria of the diagnostics and results of treatment of children with growth hormone deficiency. Effectiveness of treatment of children with above mentioned deficiency depends on the status of the patient at the time of treatment and on the dose and schedule of administration of recombinant growth hormone. Significant increase in IGF -1 and IGF – binding protein – 3 is seen in the process of treatment with growth hormone in comparison with their background values allows us to use them not only as diagnostic criteria of growth hormone deficiency but also as criteria of effectiveness of treatment with growth hormone as well.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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