DeCure for Hypogonadotropic hypogonadism 2 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 2 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 2 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 2 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
fibroblast growth factor receptor 1 (FGFR1) — FGFR1 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 4-methylpiperazin-1-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5A46 · 2.63 Å · ligand 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one (38O). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 study identified mutations in the gonadotropin-releasing hormone receptor gene in a family with hypogonadotropic hypogonadism, but noted that no abnormality of the GnRH gene itself had been found in several patients with the idiopathic form. Earlier case reports from 1966 and 1968 described the association of hypogonadotropic hypogonadism with lifelong anosmia, and the 1968 paper reported two brothers and a half-sister with the full syndrome, all related through the same mother, suggesting X-linked inheritance. A 1972 report described a 58-year-old man with anosmia and primary testicular failure who secreted elevated levels of gonadotrophin, which the authors interpreted as evidence that the hypogonadotrophism in Kallmann's syndrome is not caused by anosmia alone but involves other, probably hypothalamic, factors.
A 2014 review stated that modern diagnostics of hypogonadism rely on X-ray and laboratory investigations, which reveal the idiopathic form in the majority of patients. The review noted that recent studies had demonstrated a number of genes whose disturbed function may be responsible for the development of hypogonadism, creating prerequisites for extending diagnostics through genotyping. No drug treatment or intervention was tested or reported in any of these abstracts.
What is still missing is any clinical trial of a drug for this condition, any systematic patient stratification by genotype, and the funding to move from genetic association studies to interventional studies that could test whether specific mutations predict response to any existing therapy.
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 · 1997 · 529 citations · open access
A Family with Hypogonadotropic Hypogonadism and Mutations in the Gonadotropin-Releasing Hormone Receptor
AbstractHypogonadotropic hypogonadism is often associated with anosmia in a condition known as Kallmann's syndrome. The gene for the X-linked form of Kallmann's syndrome has been mapped to chromosome Xp22.3,1 and several mutations have been described.2–4 In idiopathic hypogonadotropic hypogonadism there is no anosmia, and the involved genes have not been characterized. One possible candidate is the gene for gonadotropin-releasing hormone (GnRH), especially since hypogonadal mice with the deletion of this gene have been identified.5 However, no abnormality of the gene for GnRH has been found in several patients with idiopathic hypogonadotropic hypogonadism.6–9 The gene for the GnRH receptor . . .
Postgraduate Medical Journal · 1966 · 14 citations · open access
Hypogonadism and life-long anosmia
AbstractJournal Article Hypogonadism and life-long anosmia Get access T D R Hockaday, MA, BM, BSc (Oxon), MRCP (Lond) T D R Hockaday, MA, BM, BSc (Oxon), MRCP (Lond) Lecturer in Medicine Department of the Regius Professor of Medicine, Radcliffe Infirmary, Oxford Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 42, Issue 491, September 1966, Pages 572–574, https://doi.org/10.1136/pgmj.42.491.572 Published: 01 September 1966
Archives of Internal Medicine · 1968 · 14 citations
Familial hypogonadotropic hypogonadism with anosmia
AbstractHypogonadotropic hypogonadism with anosmia has been found in two brothers and a half sister, who are related through the same mother. Although the mother does not have the full syndrome, her history suggests she may have minor symptoms of the syndrome. X-linked inheritance seems most compatible with the familial distributions. Differences of this syndrome from other inherited hypogonadal conditions are discussed. The genetic defect is thought to directly or indirectly affect the hypothalamus which has associations with both olfaction and pituitary function. The importance of testing for anosmia in patients with abnormality in sexual development is noted.
European Journal of Endocrinology · 1972 · 6 citations
HYPERGONADOTROPHIC HYPOGONADISM WITH ANOSMIA
AbstractABSTRACT A 58 year old male with anosmia and primary testicular failure is described. The presence of anosmia did not preclude the secretion of elevated levels of gonadotrophin suggesting that in hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) the hypogonadotrophism is not the result of anosmia alone, but that other, probably hypothalamic, factors are involved. The patient described phenotypically resembled Klinefelter's syndrome, but no chromosomal abnormality was detected. To our knowledge, hypergonadotrophic hypogonadism associated with anosmia has not previously been reported, and thus may represent a heretofore unrecognized clinical entity.
Problems of Endocrinology · 2014 · 4 citations · open access
The role of the genetic factors in pathogenesis of hypogonadotropic hypogonadism
AbstractModern diagnostics of hypogonadism is based on the results of X-ray and laboratory (biochemical) investigations that reveal the idiopathic form of the disease in the majority of the patients. However, the recent studies have demonstrated a number of genes, whose disturbed function may be responsible for the development of hypogonadism. This creates the prerequisites for the extension of diagnostics of hypogonadism by means of genotyping of the various forms of the pathology in question and thereby may facilitate the choice of the relevant treatment strategy. The present review is focused on the elucidation of the pathogenetic role of candidate genes involved in the development of isolated hypogonadotropic hypogonadism.
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.
