DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 60 — 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 moduleSpermatogenic failure 60 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 spermatogenic failure 60 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 review of 8879 vasectomies performed by one physician over 24 years found 97 failures of all types in a subgroup of 5331 men who returned for at least two postoperative semen tests. Early and overt failures occurred in 32 men (0.60%), and technical failures involving persistent small numbers of spermatozoa occurred in 61 men (1.14%). Four late overt failures (0.08%) were discovered because of a pregnancy, each at least four years after two azoospermic test results. Four failures were attributed to missed vasa deferentia, and the remainder to recanalisation.
In a 2020 age-matched case-control study of 10 patients with Klinefelter syndrome and 10 controls, GPR56 gene expression in peripheral blood mononuclear cells was down-regulated by -2081-fold (q-value <0.05) in patients compared to controls, as measured by next-generation sequencing and confirmed by QRT-PCR. The authors state that the possible contribution of this down-regulation to the pathogenesis of spermatogenic failure in Klinefelter syndrome is worthy of further exploration.
A 2008 report describes the use of clomiphene citrate prior to sperm retrieval in cases of suspected spermatogenic dysfunction. After an average of four months of clomiphene citrate targeted to increase serum testosterone above 600 ng/dl, sufficient sperm for intracytoplasmic sperm injection were observed in the ejaculate of many men. In men who remained azoospermic, the change in histological pattern within the testis favoured increased sperm yield from microsurgical testis sperm extraction.
What is missing is a clear molecular target for spermatogenic failure 60, a validated biomarker to stratify patients who might respond to hormonal stimulation, and a prospective trial that tests any intervention against a control group with standardised semen analysis endpoints.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA · 1988 · 46 citations
The lurking sperm. A review of failures in 8879 vasectomies performed by one physician
AbstractVasectomy techniques and failure rates vary among surgeons, and the criteria for failure are not often clearly defined. To help establish a yardstick for comparative purposes, a series of 8879 consecutive vasectomies performed with uniform technique over 24 years was reviewed. A subgroup of 5331 men who had returned for at least two postoperative semen tests--the study group--was used for follow-up analysis. Failures were defined as early or late and also were categorized as overt or technical according to the numbers, motility, or persistence of the remaining spermatozoa. There were 97 failures of all types, including 32 (0.60%) early and overt failures and 61 (1.14%) technical failures that involved the persistence of small numbers of spermatozoa, possibly of no significance. Four (0.08%) late overt failures were also seen; each of these was discovered as a result of a pregnancy, and each occurred at least four years after two azoospermic test results. Of the 97 failures, four were recognized as due to missed vasa deferentia, and the remainder were attributed to recanalization. Whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear.
GPR56 gene down-regulation in patients with Klinefelter syndrome: a candidate for infertility?
AbstractBACKGROUND: The etiology of azoospermia in patients with Klinefelter Syndrome (KS) is still unknown. The protein codified by the G protein-couple receptor 56 (GPR56) belongs to the adhesion family of G protein-coupled receptors (GPRs). Its mutations are involved in the pathogenesis of intellectual disability and, according to animal studies, infertility. As the expression of GPR56 in patients with KS has not been investigated so far, this study was undertaken with the purpose of evaluating its expression in peripheral blood mononuclear cells (PBMCs) of patients with KS and normal controls. METHODS: This age-matched case-control study was performed in 10 patients with KS and 10 controls. Patients and controls underwent to blood sampling for next-generation sequencing (NGS) analysis, and differentially expressed mRNAs were identified using DESeq2 v.1.12. QRT-PCR was used to validate the results obtained by NGS analysis. TaqMan Gene Expression Assay primers were used to carry out the real-time PCR analysis for GPR56. RESULTS: GPR56 was down-regulated by -2081-fold (q-value <0.05) in PBMCs of patients with KS compared to controls. NGS data were confirmed by QRT-PCR. CONCLUSIONS: The possible contribution of the GPR56 gene down-regulation in the pathogenesis of spermatogenic failure in patients with KS is worthy to be further explored.
AbstractWe studied and reported the use of clomiphene citrate prior to obtaining sperm in cases of suspected spermatogenic dysfunction (Hussein et al, J Androl 26(6), 787-91, Nov-Dec 2005.) After an average of four months of clomiphene citrate targeted to increase serum testosterone above 600 ng/dl, sufficient sperm for ICSI were observed in the ejaculate of many men. In cases where men remain azoospermic, the change in histological pattern within the testis favored increased sperm yield from microsurgical testis sperm extraction.
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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