DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 61 — screening already-approved drugs against its 2-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 61 maps to a 2-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 61 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 not been consistently shown to work. A 2011 review states that treatment with hormones or nutritional antioxidants remains largely ineffective, that no treatments have demonstrated consistent efficacy, and that it has not been possible to reliably identify which patients might benefit. The review notes that empiric medical therapy has been largely replaced by assisted reproductive techniques.
A 1988 study of 8879 vasectomies performed by one surgeon found 97 failures overall, including 32 early overt failures (0.60%) and 61 technical failures involving persistent small numbers of sperm (1.14%). Four late overt failures (0.08%) were discovered only because a pregnancy occurred, each at least four years after two azoospermic test results. Most failures were attributed to recanalisation; four were due to missed vasa deferentia.
A 2018 study of 64 Egyptian men with idiopathic non-obstructed azoospermia found that 15.6% had AZFc microdeletions, with 10% showing DAZ1/2 deletion. No T54A variant in the DAZL gene was found. The authors concluded that the spermatogenic impairment phenotype seen with AZFc microdeletions is independent of the DAZL T54A variant, and that AZFc microdeletions could be a causative agent.
A 2013 conference abstract describes work to optimise an array comparative genomic hybridisation protocol on single human sperm, not to report percentages of alterations. The authors note future applications might give information on sperm chromosome aberrations in infertile men, but no results for spermatogenic failure are given.
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.
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.
The Application of Clinical Genetics · 2018 · 4 citations · open access
Independent of DAZL-T54A variant and AZF microdeletion in a sample of Egyptian patients with idiopathic non-obstructed azoospermia
AbstractBackground: The microdeletion events that occur in the Y chromosome-azoospermia factor ( AZF ) region may lead to dyszoospermia. Also, the deleted azoospermia ( DAZ ) gene on AZFc and autosomal deleted azoospermia like gene ( DAZL ) are suggested to represent impairment, so it is interesting to determine the independency pattern of the AZF region and DAZL gene in azoospermic patients. Aim: To study the molecular characterization of AZFc and DAZL in 64 idiopathic non-obstructed azoospermia patients and 30 sexually reproductive men. Methods: SYBR Green I (Q-PCR) and AZF -STS analysis was used for DAZ gene, and SNV-PCR and confirmative Sanger sequencing for DAZL gene. Results: The present study observed that 15.6% had AZFc microdeletion, out of which 10% had DAZ1/2 deletion, and no T54A variant in the DAZL gene was found. Conclusion: In the current work, the novelty is that spermatogenic impairment phenotype, present with AZFc microdeletions, is independent of the T54A variant in the DAZL gene, and AZFc microdeletions could be a causative agent in spermatogenic impairment. Keywords: male infertility, azoospermia, AZF, DAZL, deletion
Journal of Occupational and Environmental Medicine · 2024 · 2 citations · open access
Occupational Exposure to 50 ppm Isoflurane Impairs Sperm Parameters in Mice
AbstractOBJECTIVES: The aims of the study are to assess the effect of occupational exposure to isoflurane on the sperm quality of mice and to investigate whether cessation of exposure can restore seminal quality. METHODS: Mice were exposed to 50 ppm of isoflurane for 5 hours per day over a 30-day period. Following this exposure, they were euthanized at predetermined postexposure intervals, and their sperm samples were analyzed for kinetics and viability parameters. RESULTS: Occupational exposure to isoflurane can adversely affect sperm at 50 ppm, a concentration deemed safe by international occupational health conventions in some countries. These effects are marked by oxidative stress, mitochondrial dysfunction, and genomic damage, alongside alterations in sperm kinetics and acrosomal integrity. Furthermore, cessation of exposure does not guarantee restoration of cellular quality. CONCLUSIONS: Isoflurane at 50 ppm, previously deemed safe by some countries, impairs sperm kinetics and viability, potentially directing the spermatogenic process toward infertility and apoptosis.
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
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.
