DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 18 — 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 18 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 18 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 2002 study, testicular sperm from 43 azoospermic men were analysed by FISH for numerical abnormalities of chromosomes X, Y and 18. No difference in the total frequency of chromosomal abnormalities was found between sperm from 26 men with normal spermatogenesis (5.6%) and from 17 men with spermatogenic failure (8.2%). However, aneuploidy for chromosome 18 was higher in the spermatogenic failure group (3.2%) than in the normal group (1.3%). Among the spermatogenic failure group, sex chromosome aneuploidy (5.8%) was similar to chromosome 18 aneuploidy (3.2%). The authors concluded that no difference in total chromosomal abnormality frequency had been observed between the two groups.
A 2011 review states that medical treatment of men with primary spermatogenic failure remains largely ineffective. Treatment has been attempted with hormones and nutritional supplements such as antioxidants, but 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 likely results from multiple discrete, unidentified defects in sperm production, and that empiric medical therapy has been largely replaced by assisted reproductive techniques.
Two 1988 papers report on a single surgeon’s series of 8879 vasectomies performed over 24 years. Among 5331 men who returned for at least two postoperative semen tests, there were 97 failures of all types: 32 (0.60%) early overt failures, 61 (1.14%) technical failures involving persistence of small numbers of sperm, and 4 (0.08%) late overt failures discovered because of a pregnancy at least four years after two azoospermic test results. Four failures were due to missed vasa deferentia; the remainder were attributed to recanalisation. The authors note that whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear.
What is still missing is a clear understanding of the discrete molecular defects that cause idiopathic spermatogenic failure, which would be needed to design rational therapies. No drug is mentioned in any of these abstracts as a treatment for spermatogenic failure 18 specifically. The 2011 review makes plain that no medical therapy has shown consistent efficacy, and the vasectomy papers are about surgical failure rates, not a treatment for the disease. Patient stratification by genetic cause, funding for basic discovery of the underlying defects, and properly controlled trials of any candidate agent remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Reproduction · 2002 · 101 citations
FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from azoospermic patients
AbstractBACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can successfully be used for ICSI. The concern exists that testicular sperm from azoospermic men suffering from severe testicular failure may have a higher frequency of aneuploidy, which may lead to an increased risk for chromosomally abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic failure (n = 17) and from patients with normal spermatogenesis (n = 26) were analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of 1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No difference was observed between the frequency of chromosomal abnormalities in testicular sperm from patients with normal spermatogenesis (5.6%) and from patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy for chromosome 18 was higher in the group of azoospermic patients with spermatogenic failure than in the group with normal spermatogenesis (3.2 versus 1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular sperm derived from patients with spermatogenic failure, sex chromosomal aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So far, no difference in the total frequency of chromosomal abnormalities has been observed between patients with normal spermatogenesis and patients with severe testicular failure. However, aneuploidy for chromosome 18 was higher in the group with spermatogenic failure.
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.
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)
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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