DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 47 — 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 47 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 47 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 a single physician over 24 years found 97 failures among 5331 men who returned for at least two postoperative semen tests. Failures included 32 early overt failures (0.60%), 61 technical failures involving persistent small numbers of spermatozoa (1.14%), and 4 late overt failures (0.08%) discovered because of a pregnancy at least four years after two azoospermic test results. Four failures were due to missed vasa deferentia; the rest were attributed to recanalisation.
In 41 azoospermic men with spermatogenic failure, BOULE messenger RNA transcript levels in testis tissue were significantly decreased compared to controls, and the decrease was greater with more severe testicular failure. BOULE transcript levels did not correlate with serum hormone parameters. Among 31 men who underwent sperm retrieval, the 19 with successful retrieval had significantly higher BOULE transcript levels than the 12 with failed retrieval. Using a BOULE transcript ratio cut-off of 0.5, both sensitivity and specificity for predicting successful sperm retrieval were 100%.
A 2013 study primarily aimed to optimise array comparative genomic hybridisation on single human sperm, not to report percentages of chromosomal alterations in normal or pathological conditions. The authors noted future applications might include studying sperm chromosome aberrations in infertile men, carriers of karyotype anomalies, men of advanced age, chemotherapy patients, and couples with repeated miscarriage or repeated assisted reproduction failure.
A 2023 review classifies spermatogenic failure into three subtypes: focal, arrested, and exhausted. The arrested type is attributed to genetic factors including chromosomal abnormalities, copy number variations, and single nucleotide mutations. The authors propose using whole-exome sequencing to screen patients and suggest frontier treatments such as endocrine neoadjuvant therapy and targeted therapy, but state there is still no unified or standardised clinical treatment strategy. What remains missing are large-scale prospective trials that stratify patients by genetic subtype, funding for such trials, and validated clinical protocols for the proposed endocrine and targeted therapies.
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.
Messenger RNA transcripts of the meiotic regulator BOULE in the testis of azoospermic men and their application in predicting the success of sperm retrieval
AbstractBACKGROUND: Testicular sperm retrieval can lead to paternity for azoospermic patients with spermatogenic failure. The human BOULE gene, a meiotic regulator of germ cells, is a gene whose altered expression may be associated with sterility. We determined the levels of BOULE transcripts in the testes of azoospermic patients, and evaluated the relationship between BOULE transcript levels and patients' testicular phenotypes, clinical parameters and sperm retrieval results. METHODS AND RESULTS: BOULE transcript levels in the testes of 41 azoospermic patients were examined by quantitative competitive-reverse transcription-polymerase chain reaction. A significant decrease in BOULE transcript levels was detected in patients with spermatogenic failure, and BOULE transcript levels progressively decreased with increasing severity of testicular failure. BOULE transcript levels did not correlate with the serum hormone parameters measured. Significantly higher BOULE transcript levels were detected in 19 patients with successful sperm retrieval than in 12 patients with failed sperm retrieval. When using a cut-off value of 0.5 for BOULE transcript ratio to predict the success of sperm retrieval, both the sensitivity and specificity value were 100%. CONCLUSIONS: We suggest the BOULE transcript plays an important role in human spermatogenesis and that the levels may predict the presence of testicular sperm in patients with spermatogenic failure.
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
DOAJ (DOAJ: Directory of Open Access Journals) · 2023 · 0 citations · open access
Genetic etiology and treatment of "arrested type" spermatogenic failure
AbstractSpermatogenic failure is a severe disease in male infertility, with high clinical incidence, and seriously affects the reproductive health and population security. However, due to its significant clinical heterogeneity and genetic heterogeneity, there is still no unified and standardized clinical treatment strategy currently. Our team has innovatively classified spermatogenic failure into 3 subtypes: "focal type", "arrested type" and "exhausted type". The "arrested type" spermatogenic failure is mainly caused by genetic factors such as chromosomal abnormalities, copy number variations, and single nucleotide mutations. In this paper, we review the phenotype and genetic etiology of "arrested type" spermatogenic failure, then screen the type of patients with the aid of whole-exome sequencing and other technologies, and provide frontier treatment options such as endocrine neoadjuvant therapy and targeted therapy for endocrine neoadjuvant therapy. What's more, we discuss the establishment of a multifaceted and precise diagnosis and treatment system combined with artificial intelligence.
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.
