DeCure for Hypogonadotropic hypogonadism 14 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 14 with or without anosmia — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypogonadotropic hypogonadism 14 with or without anosmia maps to a 1-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 hypogonadotropic hypogonadism 14 with or without anosmia 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
WD repeat domain 11 (WDR11) — WDR11 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 24IP · 3.07 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective study of 50 men with idiopathic hypogonadotropic hypogonadism, five sustained reversals were identified after a mean treatment interruption of six weeks. A further ten reversals were found retrospectively. Among the 15 men whose hypogonadism reversed, four had anosmia (Kallmann syndrome). At baseline, six had absent puberty and nine had partial puberty; all had abnormal GnRH-induced luteinising hormone secretion. After discontinuation of hormonal therapy, mean serum testosterone rose from 55 ng/dL to 386 ng/dL, luteinising hormone from 2.7 to 8.5 IU/L, follicle-stimulating hormone from 2.5 to 9.5 IU/L, and testicular volume from 8 mL to 16 mL. Pulsatile LH secretion and spermatogenesis were documented. The authors concluded that about 10% of patients with either absent or partial puberty show sustained reversal, and that a brief interruption of therapy to assess reversibility is reasonable.
A separate genetic study of a large consanguineous family with five siblings affected by isolated hypogonadotropic hypogonadism and a normal GnRH receptor coding sequence identified a new locus on chromosome 19p13. All affected siblings carried a homozygous 155-nucleotide deletion in the GPR54 gene that removed the splicing acceptor site of the intron 4–exon 5 junction and part of exon 5. Unaffected family members lacked the deletion or carried it on only one allele. GPR54 encodes an orphan G protein-coupled receptor with 40% homology to galanin receptors, and its ligand is a 54-amino-acid peptide derived from the KiSS1 protein. The study concluded that loss of GPR54 function causes IHH and that GPR54 and the KiSS1-derived peptide play a previously unsuspected role in gonadotropic axis physiology.
A review of hypogonadism in girls notes that the condition can occur at any life stage and that delayed puberty should prompt genetic testing with karyotype evaluation, exclusion of pituitary hormone deficiency (especially after radiotherapy or chemotherapy), and investigation for chronic or autoimmune diseases, dysmorphic features, or anosmia. Molecular studies are also recommended. The review presents guidelines for management but provides no new trial data.
What remains missing is prospective evidence from larger, unselected cohorts to confirm the 10% reversal rate, particularly in patients with anosmia. No randomised trial has tested whether a specific drug or regimen increases the likelihood of reversal. The genetic findings for GPR54 have not yet been translated into a targeted therapy, and no stratification tool exists to predict which patients might recover endogenous function. Funding for long-term follow-up studies and for trials that systematically interrupt therapy under controlled conditions is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2007 · 413 citations · open access
Reversal of Idiopathic Hypogonadotropic Hypogonadism
AbstractBACKGROUND: Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or with a normal sense of smell, is a treatable form of male infertility caused by a congenital defect in the secretion or action of gonadotropin-releasing hormone (GnRH). Patients have absent or incomplete sexual maturation by the age of 18. Idiopathic hypogonadotropic hypogonadism was previously thought to require lifelong therapy. We describe 15 men in whom reversal of idiopathic hypogonadotropic hypogonadism was sustained after discontinuation of hormonal therapy. METHODS: We defined the sustained reversal of idiopathic hypogonadotropic hypogonadism as the presence of normal adult testosterone levels after hormonal therapy was discontinued. RESULTS: Ten sustained reversals were identified retrospectively. Five sustained reversals were identified prospectively among 50 men with idiopathic hypogonadotropic hypogonadism after a mean (+/-SD) duration of treatment interruption of 6+/-3 weeks. Of the 15 men who had a sustained reversal, 4 had anosmia. At initial evaluation, 6 men had absent puberty, 9 had partial puberty, and all had abnormal secretion of GnRH-induced luteinizing hormone. All 15 men had received previous hormonal therapy to induce virilization, fertility, or both. Among those whose hypogonadism was reversed, the mean serum level of endogenous testosterone increased from 55+/-29 ng per deciliter (1.9+/-1.0 nmol per liter) to 386+/-91 ng per deciliter (13.4+/-3.2 nmol per liter, P<0.001), the luteinizing hormone level increased from 2.7+/-2.0 to 8.5+/-4.6 IU per liter (P<0.001), the level of follicle-stimulating hormone increased from 2.5+/-1.7 to 9.5+/-12.2 IU per liter (P<0.01), and testicular volume increased from 8+/-5 to 16+/-7 ml (P<0.001). Pulsatile luteinizing hormone secretion and spermatogenesis were documented. CONCLUSIONS: Sustained reversal of normosmic idiopathic hypogonadotropic hypogonadism and the Kallmann syndrome was noted after discontinuation of treatment in about 10% of patients with either absent or partial puberty. Therefore, brief discontinuation of hormonal therapy to assess reversibility of hypogonadotropic hypogonadism is reasonable. (ClinicalTrials.gov number, NCT00392756 [ClinicalTrials.gov].).
Problem hypogonadyzmu ze szczególnym uwzględnieniem problemu u dziewcząt
AbstractHypogonadism is understood as a gonadal defect; it can occur in all periods of life – in embryos, pre-adolescent and post-adolescent children, as well as after menopause. The initial cause of hypogonadism may lie in a pathology of gonads (primary, gonadal, hypergonadotropic hypogonadism) or of the hypothalamic-pituitary system (secondary hypogonadism, hypogonadotrophic hypogonadism). Hypogonadism should be discussed together with the problem of delayed puberty. In all children with delayed puberty, genetic testing with karyotype evaluation is advisable. It is also necessary to exclude pituitary hormone deficiency, especially in children having undergone radiotherapy and/or chemotherapy; it is also necessary to exclude chronic and autoimmune diseases, with special attention brought to the presence of dysmorphic features or anosmia. Molecular studies are also of importance. Guidelines for management of hypogonadism in girls have been presented.
AbstractHypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2021 · 0 citations · open access
Clinicohormonal Parameters as a Primary Step to Differentiate Normosmic Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome in a Tertiary Care Hospital in Eastern India
AbstractIntroduction: Idiopathic hypogonadotropic hypogonadism is a rare gonadal dysgenesis in which puberty does not take place naturally. It occurs due to insufficient pulsatile secretion of Gonadotrophin-Releasing Hormone (GnRH) and the resulting Follicle-Stimulating Hormone (FSH) and Luteinising Hormone (LH) deficiency leads to absence of or delayed sexual maturation. Kallmann syndrome is an uncommon genetic disorder characterised by hypogonadotropic hypogonadism associated with anosmia or hyposmia. When anosmia is absent, the same is referred as normosmic Idiopathic Hypogonadotropic hypogonadism (nIHH). Aim: To find out the significant differences between Kallmann syndrome and nIHH based on clinical features and biochemical assessment as a primary measure to initiate the treatment early. Materials and Methods: This hospital based cross-sectional observational cohort study was conducted in Department of Endocrinology, Nilratan Sircar Medical College and Hospital, Kolkata, India. The study was done on 55 cases of IHH presenting to the department with delayed secondary sexual characteristics. Results: Out of these 55 cases, 45 (81.8%) were of nIHH and only 10 (18.2%) cases were of Kallmann Syndrome. It was found that both the conditions show male predominance. Smell abnormalities were present only in Kallmann group. The level of serum testosterone was significantly higher (p<0.05) in nIHH subjects (mean-35.59 ng/dL) than patients with Kallmann Syndrome (mean-14.90 ng/dL). Patients with Kallmann syndrome showed significantly reduced pubic and axillary hair development and absence of gonadal development. Conclusion: Absence of puberty with anosmia/hyposmia with low serum FSH and LH, drastically reduced serum testosterone, are factors that point towards the diagnosis of Kallmann syndrome even in absence of genetic study, which is helpful for initiation of hormone replacement therapy for treatment.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
