DeCure for Hypogonadotropic hypogonadism 11 with or without anosmia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hypogonadotropic hypogonadism 11 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 11 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 11 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
In a 1968 report, two brothers and a half-sister related through the same mother all had hypogonadotropic hypogonadism with anosmia; the mother had possible minor symptoms, and X-linked inheritance was considered most compatible. A 1970 case described a patient with the same syndrome whose plasma levels of follicle stimulating and luteinising hormones were low and did not rise after six weeks of clomiphene citrate. The father also had anosmia, suggesting autosomal inheritance in that family. A 1997 study noted that the gene for the X-linked form of Kallmann’s syndrome had been mapped to Xp22.3, but that no abnormality of the GnRH gene had been found in several patients with idiopathic hypogonadotropic hypogonadism without anosmia.
A 2019 case reported a 25-year-old man with severe congenital hyposmia and normal testosterone and GnRH-gonadotropin axis function at first referral. At age 48 he returned with low testosterone and inappropriately normal gonadotropins, and a GnRH test indicated a hypothalamic defect. Next generation sequencing found a rare heterozygous variant in the SPRY4 gene (c.158G>A, p.R53Q), never previously reported in this context. He was started on testosterone replacement therapy. The authors noted that genetic mutations are currently found in only 40% of IHH patients, and that characterisation of other modifying genes and environmental factors is needed.
A 2014 review stated that modern diagnostics of hypogonadism rely on X-ray and laboratory investigations, which identify an idiopathic form in most patients, but that recent studies have demonstrated a number of genes whose disturbed function may be responsible. A 2016 case described a 47-year-old man whose longstanding normochromic, normocytic anaemia proved to be the first clinical manifestation of hypogonadotropic hypogonadism caused by a giant macroprolactinoma. No drug treatment for the genetic forms of the condition is tested in these abstracts beyond clomiphene citrate, which failed to raise gonadotropins in the one patient described. What remains missing are large-scale genetic studies to identify the remaining 60% of causative mutations, prospective trials of any targeted therapy, and systematic stratification of patients by genotype and age of onset.
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 . . .
Archives of Internal Medicine · 1968 · 72 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.
The Journal of Clinical Endocrinology & Metabolism · 1970 · 29 citations
Hypogonadotropic Hypogonadism with Anosmia (Kallmann's Syndrome) Unresponsive to Clomiphene Citrate
AbstractA patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) is reported. Plasma levels of pituitary follicle stimulating and luteinizing hormones, as determined by radioimmunoassay, were low, and did not rise following administration of clomiphene citrate for 6 weeks. Anosmia in the father supports an autosomal mode of inheritance in this case.
Frontiers in Endocrinology · 2019 · 14 citations · open access
A Rare SPRY4 Gene Mutation Is Associated With Anosmia and Adult-Onset Isolated Hypogonadotropic Hypogonadism
AbstractBackground. Isolated hypogonadotropic hypogonadism (IHH) is a rare, clinically heterogeneous condition, caused by the deficient secretion or action of gonadotropin releasing hormone (GnRH). It can manifest with absent or incomplete sexual maturation, or as infertility at adult-age; in a half of cases, IHH is associated with hypo/anosmia (Kallmann syndrome). Although a growing number of genes are being related to this disease, genetic mutations are currently found only in 40% of IHH patients. Case description. Severe congenital hyposmia was diagnosed in a 25-year-old Caucasian man. The patient had no history of neonatal cryptorchidism or micropenis and had gone through and completed physiological puberty; past medical history and physical examination were unremarkable. Olfactory structures appeared hypoplasic on neuroradiological imaging, while hypothalamus, pituitary gland and stalk were normal; testosterone levels, functioning of GnRH-gonadotropin axis and other pituitary hormones’ secretion were unaffected at the time of first referral. At the age of 48, the patient returned to our clinic for sexual complaints, and the finding of low testosterone levels with inappropriately normal gonadotropin levels led to the diagnosis of hypogonadotropic hypogonadism. GnRH test was consistent with hypothalamic origin of the defect. Next generation sequencing was then performed revealing a rare heterozygous allelic variant in SPRY4 gene (c.158G>A, p.R53Q). The biological and clinical effects of this gene variant had never been reported before. A diagnosis of Kallmann syndrome was finally established, and the patient was started on testosterone replacement therapy. Conclusion. This case describes the clinical phenotype associated with a rare SPRY4 gene allelic variant, consisting in congenital severe smell defect and adult-onset IHH; in patients with apparently isolated congenital anosmia genetic analysis can be valuable to guide follow up, since IHH can manifest later in adulthood. Characterization of other modifying genes and acquired environmental factors is needed for a better understanding of the physiopathology and clinical manifestations of this disease.
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.
AbstractThe case of a 47-year-old man with longstanding normochromic, normocytic anemia, which proved to be the first clinical manifestation of hypogonadotropic hypogonadism due to a giant macroprolactinoma, is reported. In case of chronic anemia of unknown origin, hypogonadism should always be included in the differential diagnosis.
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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