DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Warsaw breakage syndrome — 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 moduleWarsaw breakage syndrome 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 warsaw breakage syndrome 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
Warsaw breakage syndrome is a rare autosomal recessive cohesinopathy caused by biallelic variants in the DDX11 gene. Across the published literature only seven cases had been reported in English by 2018, and a 2018 study added five further unrelated patients identified by whole exome sequencing. One of the variants found was a novel Saudi founder variant; all were classified as pathogenic or likely pathogenic except one initially designated a variant of unknown significance (p.Arg378Pro), which functional testing showed to markedly reduce protein stability, confirming its pathogenicity. The cardinal clinical features are severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. The 2018 study compared its five patients with the seven previously reported and concluded that while microcephaly, growth retardation, and cochlear anomalies are almost universally present, the chromosomal breakage phenotype is highly variable and can be absent in some cases. One patient also had a posterior labyrinthine anomaly in addition to cochlear hypoplasia.
A 2024 case report describes a prenatal diagnosis of Warsaw breakage syndrome in a 24-week gestation fetus with microcephaly, delayed sulcation, short corpus callosum, cerebellar vermis hypoplasia, and intrahepatic portal-systemic shunts. The couple had a history of a prior pregnancy termination due to severe intrauterine growth restriction and cerebral malformations. Whole exome sequencing identified compound heterozygous pathogenic variants (c.1403dupT, p.Ser469Valfs*32 and c.1672C>T, p.Arg558*) in the DDX11 gene, and the same variants were found in the earlier terminated fetus upon retrospective analysis. Postmortem examination confirmed the prenatal ultrasound findings. This report expands the prenatal phenotypic spectrum to include specific cerebral and extracerebral anomalies.
A separate 2024 study on Nijmegen breakage syndrome, a different autosomal recessive DNA repair disorder, reviewed 84 patients in Ukraine over 25 years. Among these, 55 (65.5%) were alive, 25 (29.8%) deceased, and 4 lost to follow-up. Median age was 11 years (range 1–34). Delayed physical development was seen in most children under ten. All children had infections; 41.3% had recurrent infections, and severe infections caused 12% of deaths. Malignancies occurred in 37.5% of patients, with lymphomas accounting for 63.3% of those, and malignancies were the most common cause of death (72% of cases). Immunoglobulin replacement therapy was given to 58.7% of patients and helped reduce the frequency and severity of severe respiratory tract infections. This study does not concern Warsaw breakage syndrome and provides no data on DDX11 or treatments for that condition.
What remains missing for Warsaw breakage syndrome is any clinical trial, any treatment data, and any systematic natural history study with a cohort large enough to stratify patients by genotype or to track outcomes beyond case reports. No drug has been tested in these patients. The breakage phenotype is inconsistent, making it difficult to use as a trial endpoint, and no biomarker has been validated. Funding for a multi-centre registry and for preclinical work on DDX11 function is 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.
American Journal of Medical Genetics Part A · 2018 · 32 citations · open access
Warsaw breakage syndrome: Further clinical and genetic delineation
AbstractWarsaw breakage syndrome (WBS) is a recently recognized DDX11-related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype and genotype of this interesting condition is limited. We provide clinical and molecular information on five additional unrelated patients carrying novel bi-allelic variants in the DDX11 gene, identified via whole exome sequencing. One of the variants was found to be a novel Saudi founder variant. All identified variants were classified as pathogenic or likely pathogenic except for one that was initially classified as a variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization of this VOUS using heterologous expression of wild type and mutant DDX11 revealed a marked effect on protein stability, thus confirming pathogenicity of this variant. The phenotypic data of the seven WBS reported patients were compared to our patients for further phenotypic delineation. Although all the reported patients had cochlear hypoplasia, one patient also had posterior labyrinthine anomaly. We conclude that while the cardinal clinical features in WBS (microcephaly, growth retardation, and cochlear anomalies) are almost universally present, the breakage phenotype is highly variable and can be absent in some cases. This report further expands the knowledge of the phenotypic and molecular features of WBS.
Frontiers in Immunology · 2024 · 13 citations · open access
Nijmegen breakage syndrome: 25-year experience of diagnosis and treatment in Ukraine
AbstractIntroduction: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, characterized by microcephaly, immunodeficiency, and impaired DNA repair. NBS is most prevalent among Slavic populations, including Ukraine. Our study aimed to comprehensively assess the prevalence, diagnosis, clinical data, immunological parameters, and treatment of NBS patients in Ukraine. Methods: We conducted a retrospective review that included 84 NBS patients from different regions of Ukraine who were diagnosed in 1999-2023. Data from the Ukrainian Registry of NBS and information from treating physicians, obtained using a developed questionnaire, were utilized for analysis. Results: Among 84 NBS patients, 55 (65.5%) were alive, 25 (29.8%) deceased, and 4 were lost to follow-up. The median age of patients was 11 years, ranging from 1 to 34 years. Most patients originate from western regions of Ukraine (57.8%), although in recent years, there has been an increase in diagnoses from central and southeastern regions, expanding our knowledge of NBS prevalence. The number of diagnosed patients per year averaged 3.4 and increased from 2.7 to 4.8 in recent years. The median age of NBS diagnosis was 4.0 years (range 0.1-16) in 1999-2007 and decreased to 2.7 in the past 6 years. Delayed physical development was observed in the majority of children up to the age of ten years. All children experienced infections, and 41.3% of them had recurrent infections. Severe infections were the cause of death in 12%. The second most common clinical manifestation of NBS was malignancies (37.5%), with the prevalence of lymphomas (63.3%). Malignancies have been the most common cause of death in NBS patients (72% of cases). Decreased levels of CD4+ and CD19+ were observed in 89.6%, followed by a reduction of CD3+ (81.8%) and CD8+ (62.5%). The level of NK cells was elevated at 62.5%. IgG concentration was decreased in 72.9%, and IgA - in 56.3%. Immunoglobulin replacement therapy was administered to 58.7% of patients. Regular immunoglobulin replacement therapy has helped reduce the frequency and severity of severe respiratory tract infections. Conclusion: Improvements in diagnosis, including prenatal screening, newborn screening, monitoring, and expanding treatment options, will lead to better outcomes for NBS patients.
Prenatal Diagnosis · 2024 · 1 citations · open access
Prenatal Diagnosis of Warsaw Breakage Syndrome: Fetal Compound Heterozygous Variants in the <i>DDX11</i> Gene Associated With Growth Restriction, Cerebral, and Extra‐Cerebral Malformations
AbstractWarsaw Breakage Syndrome (WABS) is a rare autosomal recessive cohesinopathy characterized by growth retardation and congenital anomalies. This report aims to highlight the prenatal diagnosis of WABS through ultrasound findings and genetic testing. We report a case of prenatal diagnosis of WABS in a 24-week gestation fetus exhibiting microcephaly, delayed sulcation, short corpus callosum, cerebellar vermis hypoplasia and intrahepatic portal-systemic shunts. The couple had a history of a prior pregnancy termination due to severe intrauterine growth restriction and cerebral malformations. Whole exome sequencing revealed compound heterozygous pathogenic variants [NM_030653.4:c.1403dupT, p.(Ser469Valfs*32) and c.1672C>T, p.(Arg558*)] in the DDX11 gene, consistent with WABS. The same pathogenic variants were identified in the prior terminated fetus upon subsequent analysis. Postmortem examination of the proband confirmed the prenatal ultrasound findings. This case expands the understanding of the prenatal phenotypic spectrum of WABS by identifying specific cerebral and extracerebral anomalies associated with pathogenic variants in the DDX11 gene. Incorporating advanced genetic diagnostics like whole exome sequencing into prenatal care provides valuable information for genetic counseling and management of rare genetic disorders.
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.
