DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for xeroderma pigmentosum group F — 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 moduleXeroderma pigmentosum group F 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 xeroderma pigmentosum group f 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
ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) — ERCC4 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 sf4drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9PD3 · 3.3 Å · ligand IRON/SULFUR CLUSTER (SF4). Experimental structure, not a prediction.
What the evidence adds up to
In 29 Japanese xeroderma pigmentosum group A patients, 86% (25 patients) carried a homozygous splicing mutation at the junction of intron 3 and exon 4 of the XPA gene. Those with that homozygous mutation developed severe skin manifestations from early infancy and severe progressive neurological abnormalities including sensorineural hearing loss, brain atrophy, mental retardation, areflexia, and ataxia. Four patients were heterozygous for that splicing mutation; at least three of them had milder skin and neurological symptoms. Two patients (identical twins) were compound heterozygotes for the intron 3 splicing mutation and a nonsense mutation in exon 6. One patient had the splicing mutation plus a previously unreported mutation at the last codon of exon 5. The authors concluded that different genetic alterations in the XPA gene produce different clinical features.
A separate series of 11 XP patients with head and neck cutaneous malignancies, treated between 2005 and 2015, had a mean age of 32 years (range 10–43; 4 males, 7 females). Squamous cell carcinoma was the most common tumour type (6 patients) and the orbital region the most common location (4 patients). Free tissue transfer was the most frequent surgical intervention (4 patients). The average number of surgical procedures per patient was 5.5 (range 1–25). Six patients were siblings, five had local recurrences, and one was lost to follow-up. The authors stated that no definitive treatment algorithm exists, that early surgery and close follow-up remain the standard because of rapid tumour growth and frequent recurrence, and that treatment must be individualised.
A 2023 study from southern Morocco described XP as a rare autosomal recessive dermatosis relatively frequent in countries with high consanguinity, characterised by photo-induced skin changes, ocular lesions, and sometimes neurological involvement. It specified that the aim was to present epidemiological, clinical, and histological profiles of XP patients treated in a plastic surgery department, and to describe the modalities of oncologic and reparative surgical treatment. No patient numbers, response rates, or survival data were given in that abstract.
What is still missing: prospective trials comparing surgical approaches, any systemic therapy tested in XP, validated methods to stratify patients by genotype for treatment decisions, and funding for multi-centre registries that could generate enough data to move beyond case series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Dermatology · 1994 · 91 citations
Gene Alterations and Clinical Characteristics of Xeroderma Pigmentosum Group A Patients in Japan
AbstractBACKGROUND AND DESIGN: The responsible gene for xeroderma pigmentosum group A was recently identified. This study was performed to detect the gene alteration of xeroderma pigmentosum group A complementing gene in 29 xeroderma pigmentosum group A patients in Japan and to analyze whether genetic alterations in the xeroderma pigmentosum group A complementing gene are related to the clinical features. RESULTS: Of 29 patients, 25 (86%) had a mutation at the splicing junction of intron 3 and exon 4 in the homozygous state that was detected by the polymerase chain reaction and the AlwN I-restriction fragment length polymorphism. Patients having a splicing mutation at intron 3 in the homozygous state develop severe skin manifestations from early infancy and severe progressive neurologic abnormalities, including sensorineural hearing impairment, brain atrophy, mental retardation, areflexia, and ataxia. Four patients were heterozygous for splicing mutation in intron 3. Among them, at least three patients showed milder skin symptoms and milder neurologic abnormalities than patients with the homozygous splicing mutation. Two patients (single-ovum twins) revealed a compound heterozygote of splicing mutation of intron 3 and a nonsense mutation of exon 6. One patient had the splicing mutation and another mutation at the last codon of exon 5, a type of mutation that has never been reported. CONCLUSION: These data indicate that different genetic alterations in the xeroderma pigmentosum group A complementing gene may induce different clinical features.
Archives of Plastic Surgery · 2016 · 9 citations · open access
Technical Aspects and Difficulties in the Management of Head and Neck Cutaneous Malignancies in Xeroderma Pigmentosum
AbstractBACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by xerosis, ultraviolet light sensitivity, and cutaneous dyspigmentation. Due to defects in their DNA repair mechanism, genetic mutations and carcinogenesis inevitably occurs in almost all patients. In these patients, reconstruction of cutaneous malignancies in the head and neck area is associated with some challenges such as likelihood of recurrence and an aggressive clinical course. The aim of this study is to discuss the therapeutic options and challenges commonly seen during the course of treatment. METHODS: Between 2005 and 2015, 11 XP patients with head and neck cutaneous malignancies were included in this study. Demographic data and treatment options of the patients were evaluated. RESULTS: The mean age of the patients was 32 years (range, 10-43) (4 males, 7 females). The most common tumor type and location were squamous cell carcinoma (6 patients) and the orbital region (4 patients), respectively. Free tissue transfer was the most commonly performed surgical intervention (4 patients). The average number of surgical procedures was 5.5 (range, 1-25). Six patients were siblings with each other, 5 patients had local recurrences, and one patient was lost to follow-up. CONCLUSIONS: Although genetic components of the disease have been elucidated, there is no definitive treatment algorithm. Early surgical intervention and close follow-up are the gold standard modalities due to the tendency toward rapid tumor growth and possible recurrence. Treatment must be individualized for each patient. In addition, the psychological aspect of the disease is an important issue for both patients and families.
Journal of Pigmentary Disorders · 2015 · 6 citations
Xeroderma Pigmentosum-A Rare Genodermatosis: Overview of Literature
AbstractXeroderma pigmentosum is a rare genodermatosis, autosomal recessive in nature in which excessive ultraviolet radiation causes skin, ocular, neurological, and oral lesions along with development of cutaneous and internal malignancies at an early age. There is no definitive cure for the disease. Avoidance of ultraviolet radiation, use of protective clothing, sunscreens, oral retinoids, 5-fluorouracil and regular consultations with dermatologists, ophthalmologists, neurologists and dentists forms an important part of the treatment protocol. This paper aims to throw light on the etiopathogenesis, clinical features and treatment modalities of this life threatening disease. There is also a special mention on the oral manifestations and dental health considerations of the rare disorder.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
XERODERMAPIGMENTOSUM: EPIDEMIOLOGICAL, CLINICAL AND THERAPEUTIC ASPECTS
AbstractXeroderma Pigmentosum (XP) is a rare and disabling genetic dermatosis that was first described in 1874. It is characterized by photo-induced cutaneous alterations, often associated with ocular lesions and sometimes with neurological involvement. The transmission of XP is on an autosomal recessive mode, and it is relatively frequent in countries with high consanguinity rates and large family sizes, such as those in the Maghreb region. This study aims to present an epidemiological, clinical, and histological profile of XP patients treated in the plastic surgery department in southern Morocco, reflecting the regions epidemiological reality and specifying the modalities of oncologic and reparative surgical treatment.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
XERODERMAPIGMENTOSUM: EPIDEMIOLOGICAL, CLINICAL AND THERAPEUTIC ASPECTS
AbstractXeroderma Pigmentosum (XP) is a rare and disabling genetic dermatosis that was first described in 1874. It is characterized by photo-induced cutaneous alterations, often associated with ocular lesions and sometimes with neurological involvement. The transmission of XP is on an autosomal recessive mode, and it is relatively frequent in countries with high consanguinity rates and large family sizes, such as those in the Maghreb region. This study aims to present an epidemiological, clinical, and histological profile of XP patients treated in the plastic surgery department in southern Morocco, reflecting the regions epidemiological reality and specifying the modalities of oncologic and reparative surgical treatment.
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.
