DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 45 — 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 45 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 45 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
Medical therapy for primary spermatogenic failure has been attempted with hormones and nutritional antioxidants, but a 2011 review states that no treatments have consistently demonstrated efficacy and it has not been possible to reliably identify patients likely to benefit. The review notes that idiopathic spermatogenic failure probably results from multiple discrete defects in sperm production that remain unidentified, and that empiric medical therapy has been largely replaced by assisted reproductive techniques.
A 2020 case-control study of 10 patients with Klinefelter syndrome and 10 controls found that the GPR56 gene was down-regulated by -2081-fold in peripheral blood mononuclear cells of patients compared to controls. The authors suggest the possible contribution of this down-regulation to the pathogenesis of spermatogenic failure in Klinefelter syndrome is worthy of further exploration, but no therapeutic intervention was tested.
A 1988 review of 8879 consecutive vasectomies performed with uniform technique over 24 years reported 97 failures of all types, including 32 early overt failures (0.60%), 61 technical failures involving persistence of small numbers of spermatozoa (1.14%), and 4 late overt failures (0.08%) each discovered because of a pregnancy occurring at least four years after two azoospermic test results. Four failures were due to missed vasa deferentia and the remainder were attributed to recanalisation.
A 2013 study optimising aCGH protocols on single sperm notes that future application might give information on sperm chromosome aberrations in infertile men, but the study was not designed to provide percentages of alterations in normal or pathological conditions. What is still missing is identification of the discrete molecular defects underlying idiopathic spermatogenic failure, reliable biomarkers to triage patients to specific regimens, and adequately powered trials of any candidate 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.
Asian Journal of Andrology · 2011 · 57 citations · open access
Medical therapy for spermatogenic failure
AbstractMedical treatment of men with primary spermatogenic failure remains largely ineffective in contrast to those with secondary testicular failure. Treatment has been attempted with a multitude of agents ranging from hormones to nutritional supplements (antioxidants). While some studies have demonstrated benefit to some treatments, no treatments have consistently demonstrated efficacy nor has it been possible to reliably identify patients likely to benefit. Idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. This review focuses on the rationale and current evidence for hormonal and antioxidant therapy in medical treatment of male infertility, spermatogenic failure in particular. Although empiric medical therapy for spermatogenic failure has been largely replaced by assisted reproductive techniques, both treatment modalities could play a role, perhaps as combination therapy.
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<i>study</i>group—was used for follow-up analysis. Failures were defined as<i>early</i>or<i>late</i>and also were categorized as overt or<i>technical</i>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. (<i>JAMA</i>1988;259:3142-3144)
International Journal of Nanomedicine · 2024 · 6 citations · open access
Eugenol Nanoparticles Ameliorate Doxorubicin-Induced Spermatogenic Dysfunction by Inhibiting the PINK1/Parkin and BNIP3/NIX Signaling Pathways
AbstractPurpose: Doxorubicin (DOX) precipitates cell apoptosis in testicular tissues, and it is imperative to develop drugs to alleviate the spermatogenic disorders it causes. Eugenia caryophyllata Thunb is often used to treat male sexual disorders. Eugenol, a major component of Eugenia caryophyllata Thunb. has inadequate stability and low solubility, which limits its pharmacological effects. Eugenol nanoparticles (NPs) (ENPs) are expected to overcome these limitations. The protective effects of ENPs against DOX-induced reproductive toxicity were studied in mice. Methods: Eugenol was encapsulated in Methoxy-Poly(ethylene glycol)-Poly(lactide-co-glycolide) nanoparticles (mPEG-PLGA-NPs), and their role in ameliorating spermatogenic dysfunction was verified in vivo and in vitro. Results: We present a promising delivery system that encapsulates eugenol into mPEG-PLGA-NPs and forms them into nanocomposites. In vitro, ENPs significantly reduced doxorubicin-induced ROS and inflammatory factors in GC-1 cells and regulated the expression of the mitochondrial autophagy protein PINK1 and meiosis-related protein SCP3. In vivo, ENPs significantly increased sperm motility in mice, reduced apoptosis and oxidative stress in the testes, inhibited the testicular PINK1/Parkin and BNIP3/NIX signaling pathways, and enhanced the expression of factors associated with meiosis. Conclusion: Given their safety and efficacy, these ENPs have potential application prospects in mitigating doxorubicin-induced spermatogenic dysfunction. Keywords: Eugenol nanoparticles, Doxorubicin, spermatogenic dysfunction, PINK1/Parkin and BNIP3/NIX signaling pathways, Mitochondrial autophagy
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.
Human Reproduction · 2013 · 0 citations · open access
Session 69: Clinical endocrinology
AbstractLimitations, reason for caution: This study was mainly performed to optimize an aCGH protocol on human single sperm, not to have percentage of alterations in normal and pathological conditions. Wider implications of the findings: Future application of this method might give important information on the biology and pathophysiology of spermatogenesis and sperm chromosome aberrations in normal subjects and in patients at higher risk of producing unbalanced sperm, such as infertile men, carriers of karyotype anomalies, men with advanced age, subjects treated with chemotherapy, and partners of couples with repeated miscarriage and repeated failure during assisted reproduction techniques. Study funding/competing interest(s): University of Padova/no competing interests
AbstractSubfertility, defined as the inability to conceive within I year of unprotected intercourse, affects 10-15% of couples. in up to 55%, of couples, the male partner is diagnosed with spermatogenic failure, i.e. one or more semen parameters fall below the WHO criteria for normozoospermia. In these cases, assisted reproductive technology is usually used to achieve pregnancy. Both genetic and environmental factors are thought to underlie spermatogenic failure. Despite years of research, only few genetic factors have clearly been shown to cause spermatogenic failure, and the identification of additional genetic causes or risk factors has proven to be extremely difficult. in this review, we will present an overview of established genetic causes of spermatogenic failure, describe pitfalls in searching for novel genetic factors and discuss research opportunities for the future. Reproduction (2010) 139 303-307
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.
