DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Woodhouse-Sakati syndrome — 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 moduleWoodhouse-Sakati syndrome 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 woodhouse-sakati 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
Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterised by hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. It is caused by mutation of the C2orf37 gene, now referred to as DCAF17. A 2010 study of seven new cases from three ethnic backgrounds identified a novel mutation in each of four families investigated: three nonsense mutations and one splice site ablation. That study doubled the number of known mutations for the disorder and confirmed that truncating mutations in C2orf37 are the only known cause of WSS. In a separate collection of 11 cases presenting only with deafness and dystonia, no pathogenic changes were found, suggesting that mutations in this gene do not contribute significantly to isolated elements of WSS. The lack of correlation between the site of the eight truncating mutations and clinical expressivity strongly supported that they are equally null, while intrafamilial variability argued for an important role of modifiers.
A 2023 systematic review covering the literature up to June 2022 identified 25 eligible studies, comprising 185 patients in 97 families from 12 different countries. In patients from the Greater Middle East region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development, including eight identified in the Greater Middle East region. The most frequent variant was a frameshift deletion (c.436delC, p.Ala147Hisfs*9) unique to Arabs, reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain and Saudi Arabia. The review found no clear genotype-phenotype correlations for the different variants.
No drug treatment, repurposed or otherwise, is mentioned in any of these abstracts. No clinical trial of any therapeutic agent for Woodhouse-Sakati syndrome is reported. What is missing is any interventional study design, any patient stratification strategy, and any funding directed toward testing a candidate drug in this population. The genetic basis is increasingly well described, but the step from genetic diagnosis to therapy has not been taken.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 2010 · 48 citations
<i>C2orf37</i> mutational spectrum in Woodhouse–Sakati syndrome patients
AbstractWoodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.
Orphanet Journal of Rare Diseases · 2023 · 10 citations · open access
Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review
AbstractBACKGROUND: Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease. METHODS: PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are "Woodhouse Sakati" along with the term "mutation" OR "gene" OR "variant" OR "polymorphism". RESULTS: Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype-phenotype correlations for the different variants. CONCLUSIONS: This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype-phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients.
Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review
AbstractAbstract Background Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease. Methods PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are “Woodhouse Sakati” along with the term “mutation” OR “gene” OR “variant” OR “polymorphism”. Results Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype–phenotype correlations for the different variants. Conclusions This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype–phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients.
Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review
AbstractAbstract Background Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. The aim of this study was to systematically review the genetic basis of WSS and report the genetic variants and clinical phenotypes associated with the disease. Methods PubMed, Science Direct, Scopus, and Web of Science databases were searched from the time of inception until June 2022. Broad search terms were used to capture the literature describing all genetic variants associated with WSS. The search keywords used are “Woodhouse Sakati” along with the term “mutation” OR “gene” OR “variant” OR “polymorphism”. Results Twenty-five eligible studies were included in this study. One hundred and eighty-five patients in 97 families from 12 different countries were diagnosed with WSS. In patients from the Greater Middle East (GME) region, consanguineous marriages were common (67%). Thirteen different DCAF17 variants were associated with WSS development (including 8 identified in the GME region). The most frequent variant was a frameshift deletion variant (c.436delC, p.Ala147Hisfs*9) unique to Arabs that was reported in 11 cases from Tunisia, Kuwait, Qatar, Bahrain, and Saudi Arabia. There were no clear genotype–phenotype correlations for the different variants. Conclusions This systematic review highlights the molecular basis and clinical manifestations of WSS globally, including the GME region, where the disease is prevalent due to consanguinity. Additional studies are now needed to understand the genotype–phenotype correlation for different DCAF17 variants and their impact on the phenotypic heterogeneity observed in WSS patients.
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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