DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Brooke-Spiegler syndrome — 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 moduleBrooke-Spiegler syndrome 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 brooke-spiegler 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.
Molecular view
glycoprotein Ib platelet subunit alpha (GP1BA) — GP1BA 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 cacdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4C2A · 2.081 Å · ligand CACODYLATE ION (CAC). Experimental structure, not a prediction.
What the evidence adds up to
Brooke-Spiegler syndrome is a rare autosomal dominant genetic disorder caused by mutations in the CYLD gene on chromosome 16q12–13. The CYLD protein is a deubiquitinating enzyme that negatively regulates the NF‑κB signalling pathway by removing ubiquitin from NEMO and TRAF‑2. When CYLD is inhibited, NF‑κB activation increases, leading to greater resistance to apoptosis and advanced carcinogenesis. The syndrome is characterised by multiple adnexal skin tumours — cylindromas, trichoepitheliomas, spiradenomas and spiradenocylindromas — that typically appear on the face, scalp, neck and trunk from the first or second decade of life. Malignant transformation is rare but has been reported. The incidence and prevalence are unknown, and the condition affects both sexes equally across all ethnic groups.
Three reports describe novel CYLD mutations. In 2006 a new mutation was found in a family with the syndrome. In 2015 three novel germline mutations were identified in unrelated patients: c.1821_1826+1delinsCT/L607Ffs*9, c.2666A>T/p.D889V and c.2712delT/p.905Kfs*8. In 2009 a new frameshift mutation in exon 19 was reported in another family. These findings extend the mutation spectrum but do not point to any targeted therapy.
A 2017 case report describes a female patient with a typical clinical picture and a positive family history (mother, two sisters, brother and niece). The recommended therapy was surgical treatment, which the patient declined because she feared losing her hair. A 2024 case report presents a 53‑year‑old woman with multiple pinkish firm papulonodular lesions on the central forehead and nasal area who sought cardiac consultation for palpitations; the authors emphasise the rarity of the syndrome and the need to document it.
No drug treatment is mentioned in any of these abstracts. What is missing is any clinical trial testing a medical therapy, any evidence linking specific CYLD mutations to drug response, and any patient stratification strategy. Without funding for a trial and a molecularly informed design, the management remains surgical observation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 2006 · 21 citations
A case of Brooke-Spiegler syndrome with a new mutation in the <i>CYLD</i> gene
AbstractConflicts of interest: None declared. Familial cylindromatosis (syn.: Brooke–Spiegler syndrome; MIM 132700), a rare autosomal dominant inherited disorder, is characterized by the development of multiple adnexal skin tumours (especially cylindromas, trichoepitheliomas and spiradenomas) arising from the apocrine and eccrine glands. They most commonly occur between the first and second decade of life on the face, scalp or, less frequently, neck and trunk. Malignant transformation is rare, but should be considered in clinically altered lesions. Mutations in the CYLD gene (MIM *605018; previously known as CYLD1) on chromosome 16q12–13 were identified to be responsible for the disease.1, 2 The CYLD gene spans over 56 kb of genomic DNA and contains 20 exons. Exons 4–20 encode for a product of 956 amino acids, which is expressed in different tissues. The CYLD protein, a member of the family of deubiquitinating enzymes (DUBs), contains a C‐terminal ubiquitin‐specific protease domain and plays an indispensible role in the NF‐κB signalling pathway. Post‐translational modification of proteins by attachment of ubiquitin is a common event to target them for proteasomal degradation or other cellular processes. DUBs reverse these effects by removing ubiquitin from substrate proteins. NEMO, the regulatory subunit of the inhibitor κB kinase complex, and the tumour necrosis factor receptor‐associated factor 2 (TRAF‐2), are the main targets of CYLD, which negatively regulates NF‐κB (Fig. 1). Inhibition of CYLD enhances activation of the transcription factor NF‐κB and leads to increased resistance to apoptosis and advanced carcinogenesis.3–5
Report of Three Novel Germline <b><i>CYLD</i></b> Mutations in Unrelated Patients with Brooke-Spiegler Syndrome, Including Classic Phenotype, Multiple Familial Trichoepitheliomas and Malignant Transformation
AbstractBrooke-Spiegler syndrome is a rare autosomal-dominant genetic disorder characterized by multiple adnexal tumors, including cylindromas, spiradenomas, spiradenocylindromas and trichoepitheliomas. It is caused by germline CYLD mutations commonly leading to a premature stop codon. We here report on 3 novel CYLD mutations in 3 unrelated BSS patients, including the classic phenotype, multiple familial trichoepitheliomas phenotype and malignant transformation. These included c.1821_1826+1delinsCT/L607Ffs*9, c.2666A>T/p.D889V and c.2712delT/p.905Kfs*8. By extending the spectrum of CYLD mutations, better understanding of the molecular mechanisms of BSS can be gained, which might later assist in finding new treatment options.
JDDG Journal der Deutschen Dermatologischen Gesellschaft · 2009 · 11 citations
New mutation in the CYLD gene within a family with Brooke‐Spiegler syndrome
AbstractSummary Brooke‐Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12‐q13. We describe a family, in which we performed a molecular‐genetic examination and found a new mutation in exon 19 in the CYLD gene leading to a frameshift. It is important to be aware of this syndrome and its pathogenesis as its phenotypic features can vary so that apparently different diseases are caused by the same genetic defect. In addition, there may be malignant transformation of the generally benign tumors, so that a timely diagnosis is essential for appropriate monitoring and therapy.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Brooke-Spiegler Syndrome: A Case Report
AbstractBrooke-Spiegler Syndrome (BSS or BRSS), refers to a genetic disorder marked by diverse dermatological neoplasms. BSS, found across all ethnic groups with an unknown incidence and prevalence, impacts both genders equally. A 53-year-old female diagnosed with BSS sought cardiac consultation due to complaints of palpitations. Upon examination, multiple pinkish-colored, firm papulonodular lesions were observed on mainly the central forehead and nasal area. This case is presented due to the rarity of BRSS, emphasizing the need to document and share information about this infrequently encountered syndrome.
Medicinski casopis · 2017 · 0 citations · open access
A case report of a female patient with Brooke-Spiegler syndrome
AbstractBrooke-Spiegler syndrome is a rare autosomal dominant hereditary disease with variable penetration. The syndrome is manifested by the appearance of three types of tumors: multiple cylindromas, trichoepitheliomas and spiradenomas. Tumors can cover the entire scalp in the form of turban, so Turban tumor is usually a synonym for this disease. We presented a patient with a typical clinical picture of Brooke-Spiegler syndrome, who has a positive family history (mother, two sisters, brother and niece). Recommended therapy for this syndrome is surgical treatment. She did not accept surgical treatment, because she was afraid of losing her hair.
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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