DeCure for Hypogonadotropic hypogonadism 10 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 10 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 10 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 10 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.
What the evidence adds up to
A 2003 study of a large consanguineous family with five siblings affected by isolated hypogonadotropic hypogonadism (IHH) and a normal gonadotropin-releasing hormone receptor coding sequence identified a homozygous 155-nucleotide deletion in the GPR54 gene on chromosome 19p13. The deletion removed the splicing acceptor site of the intron 4–exon 5 junction and part of exon 5, and was absent or present on only one allele in unaffected family members. GPR54 is an orphan G protein-coupled receptor with 40% homology to galanin receptors, and a 54-amino-acid peptide derived from the KiSS1 protein had recently been identified as its ligand. The study concluded that loss of function of GPR54 causes IHH and that GPR54 and possibly the KiSS1-derived peptide play a previously unsuspected major role in the gonadotropic axis.
A 2018 study of 100 HIV-infected men found an overall prevalence of hypogonadism of 66%, with 30–35% of patients reporting symptoms of hypoandrogenemia. Hypogonadotropic hypogonadism specifically was found in 42% of patients. A significant association was reported between the prevalence of hypogonadism and the level of immunodeficiency, with hypogonadism increasing as CD4 counts decreased. Lower free testosterone and dehydroepiandrosterone sulfate levels were found in cases of severe immunosuppression and correlated statistically significantly with CD4 counts. Mean free testosterone and follicle-stimulating hormone were significantly higher in patients on antiretroviral therapy than in those not on it, but no specific antiretroviral drug or combination correlated significantly with any sex hormone level. The study concluded that hypogonadotropic hypogonadism is a common endocrine disorder in HIV-infected men, seen more often with low CD4 counts.
A third abstract, from 2002, is written in Japanese and appears to concern the evaluation of S-wave velocity in ground improved by a sand compaction pile method. It contains no information relevant to hypogonadotropic hypogonadism.
What is still missing is any clinical trial testing a drug to restore GPR54 signalling in patients with IHH caused by GPR54 loss-of-function mutations. No such trial is described in these abstracts. The 2018 HIV study is observational and does not test a treatment for hypogonadotropic hypogonadism. Funding for a proof-of-concept study using a kisspeptin analogue in GPR54-deficient patients has not been reported, and no patient stratification by specific GPR54 mutation has been attempted in a treatment setting.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 2003 · 2417 citations · open access
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
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.
Indian Journal of Endocrinology and Metabolism · 2018 · 12 citations · open access
Sex hormone profile in human immunodeficiency virus-infected men and it's correlation with CD4 cell counts
AbstractBackground: In human immunodeficiency virus (HIV)-infected men, hypogonadism is the most common endocrinological disorder, and most cases of hypogonadism are secondary. The aim of this study was to find out the hormonal abnormalities in HIV-infected males and it's correlation with CD4 cell counts. Materials and Methods: One hundred HIV-infected male patients were evaluated in the Department of Medicine, Postgraduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India, over a period of 12 months from September 2014 to August 2015 using history, physical examination, routine baseline investigations, and CD4 counts. Free testosterone, dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured using an overnight fasting sample. Patients were divided into three groups on the basis of CD4 counts (Group A: CD4 counts ≥350/mm3, Group B: CD4 counts between 200 and 349/mm3, and Group C: CD4 counts <200/mm3). Data were analyzed using Student's t-test, ANOVA test, Chi-square test, and Pearson's test and P ≤ 0.05 was considered statistically significant. Results: In 100 HIV-infected males, overall prevalence of hypogonadism was found to be 66%, and 30%–35% patients had symptoms of hypoandrogenemia. Hypogonadotropic hypogonadism was found in 42% of patients. A significant association (P = 0.027) was found between prevalence of hypogonadism and the level of immunodeficiency with an increase in the prevalence of hypogonadism as CD4 counts decreased. Lower levels of free testosterone and DHEAS were found in cases of severe immunosuppression with a statistically significant correlation with CD4 counts. Correlation of other sex hormones (LH, FSH, and prolactin) with CD4 counts not statistically significant. Mean free testosterone and FSH were found to be significantly higher in patients on antiretroviral therapy (ART) than in those not on ART (P = 0.028 and P = 0.045, respectively), but no specific ART drug or their drug combination was found to have a significant correlation with levels of any sex hormone. Conclusion: Hypogonadism (hypogonadotropic hypogonadism) was found to be a common endocrinological disorder in HIV-infected male population, seen more commonly in association with low CD4 counts.
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.
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.
