DeCure for Male infertility due to globozoospermia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for male infertility due to globozoospermia — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMale infertility due to globozoospermia maps to a 3-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 male infertility due to globozoospermia 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.
Molecular view
protein interacting with PRKCA 1 (PICK1) — PICK1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 4-bromophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AR4 · 1.69 Å · ligand N-[4-(4-bromophenyl)-1-{[2-(trifluoromethyl)phenyl]methyl}piperidine-4-carbonyl]-3-cyclopropyl-L-alanine (BQA). Experimental structure, not a prediction.
What the evidence adds up to
In a 2002 study, sperm from one globozoospermic man were injected into bovine oocytes to test centrosomal function and oocyte activation ability. Sperm aster formation occurred in 15.8% of oocytes injected with his round-headed sperm, compared with 57.9% for fertile donor sperm; male pronuclear formation was 31.0% versus 92.5%. Ethanol activation after injection improved the patient’s male pronuclear formation to 84.9% but raised sperm aster formation only to 32.3%. The authors concluded that the patient’s sperm had centrosomal dysfunction and low oocyte activation ability compared with fertile donor sperm, and that the centrosomal dysfunction might be one cause of his infertility.
A 2016 study measured expression of phospholipase C zeta (PLCζ) and postacrosomal sheath WW domain binding protein (PAWP) in 21 infertile men with globozoospermia and 25 fertile men. Both PLCζ and PAWP were significantly reduced at RNA and protein levels in the globozoospermic group. The authors suggested that intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation might rescue failed fertilisation in routine ICSI for these patients.
A 2022 case report describes a 26-year-old man with total globozoospermia (100% round-headed sperm, no acrosomes) whose couple underwent ICSI with assisted oocyte activation. This resulted in the conception and birth of a healthy child. The authors note this is the first such reported case in Romania. The report does not provide data on how many cycles were attempted or the success rate in a larger series.
What is still missing are controlled trials with sufficient sample sizes to establish whether ICSI plus artificial oocyte activation reliably produces live births in globozoospermia, and whether the centrosomal dysfunction identified in 2002 is overcome by current activation protocols. Patient stratification by PLCζ or PAWP expression level has not been tested in a prospective trial. Funding for such trials remains 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 · 58 citations · open access
Analysis of the human sperm centrosomal function and the oocyte activation ability in a case of globozoospermia, by ICSI into bovine oocytes
AbstractBACKGROUND: Centrosomal function and oocyte activation ability of human sperm from a case of globozoospermia was assayed by heterologous ICSI into bovine oocytes. METHODS: Microtubules and chromatin configuration in bovine oocytes were examined by immunofluorescence after heterologous ICSI with human sperm from two fertile donors and from a globozoospermic man. RESULTS: The microtubule array from the sperm centrosome, the 'sperm aster' and the male pronucleus were observed in bovine oocytes, following ICSI with round-headed sperm from a globozoospermic man. The rate of sperm aster formation and the rate of male pronuclear formation in the bovine oocytes injected with fertile donor sperm were 57.9 and 92.5% respectively; the respective values for oocytes injected with round-headed sperm without artificial oocyte activation were 15.8 and 31.0%. Ethanol activation after ICSI improved male pronuclear formation (84.9%) but not sperm aster formation rate (32.3%) of the globozoospermic patient. CONCLUSIONS: These data indicated that sperm from this patient with globozoospermia have centrosomal dysfunction and low ability for oocyte activation compared with fertile donor sperm. The centrosomal dysfunction may be one of the reasons for infertility in this patient.
Evaluation of PLCζ and PAWP Expression in Globozoospermic Individuals.
AbstractOBJECTIVE: Globozoospermia is a rare type of teratozoospermia with incidence of 0.1% among infertile individuals. Phospholipase C zeta (PLCζ) and postacrosomal sheath WW domain binding protein (PAWP) are the main candidates in sperm taking responsibility for oocyte activation during fertilization. Therefore, we aimed to evaluate the expression of these two genes at RNA and protein levels in globozoospermic individuals and compare the results with fertile individuals. MATERIALS AND METHODS: In this experimental study, semen samples of 21 infertile men with globozoospermia and 25 fertile men were collected. Expression of PLCζ and PAWP at RNA and protein levels were assessed and compared between two groups by quantitative real time polymerase chain reaction (qPCR) and Western blot, respectively. RESULTS: Expression of both PLCζ and PAWP were significantly reduced at RNA and protein levels in infertile men with globozoospermia compared to fertile men. CONCLUSION: This is the first study that simultaneously assessing the respective factors in a large population of globozoospermia, suggested that intra-cytoplasmic sperm injection (ICSI) along with artificial oocyte activation may rescue failed fertilization in routine ICSI.
Romanian Journal of Morphology and Embryology · 2022 · 0 citations · open access
Healthy birth in a case of total globozoospermia after intracytoplasmic sperm injection and assisted oocyte activation
AbstractGlobozoospermia is a rare (incidence <0.1%) and very severe disorder, with major implications in male fertility. Total globozoospermia is represented by the presence of spermatozoa with 100% rounded heads and a lack of acrosomes. These specific morphological modifications seem to be connected to defects occurring in the last stage of spermatogenesis, spermiogenesis, and will result in anomalies of the acrosomal reaction and a defective adherence of the spermatozoa to the oocytes zona pellucida. This will result in a failure of natural fertilization. This article aims to present the case of a couple diagnosed and successfully treated for primary male infertility. The 26-year-old male partner underwent two semen analyses that revealed the presence of fully rounded spermatozoa heads (morphological abnormality) and consequently was proposed for in vitro fertilization treatment. Semen preparation and the use of assisted reproductive techniques, intracytoplasmic injection of sperm cells into the assisted oocyte activation, have resulted in the conceivement of a healthy child. The particularities of this case lie in the early recognition of the total abnormal globozoospermia morphology. This is the first case reported in Romania where specific assisted reproductive techniques and treatments have resulted in a successful pregnancy for a couple with male total globozoospermia.
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.
