DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for xeroderma pigmentosum variant type — 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 variant type 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 variant type 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
DNA polymerase eta (POLH) — POLH 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 rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6MXO · 2.04 Å · ligand 2'-deoxy-5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]cytidine (0KX). Experimental structure, not a prediction.
What the evidence adds up to
No drug treatment is tested or proposed in any of these abstracts. The 1994 study of 29 Japanese xeroderma pigmentosum group A patients found that 25 (86%) carried a homozygous splicing mutation at intron 3, which was associated with severe skin manifestations from early infancy and progressive neurological abnormalities including sensorineural hearing loss, brain atrophy, mental retardation, areflexia, and ataxia. Four patients were heterozygous for that mutation, and at least three of them had milder skin and neurological symptoms. Two patients (identical twins) were compound heterozygotes for the 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 1997 review states that the molecular basis of the variant complementation group remained to be elucidated at that time.
A 2016 surgical series of 11 XP patients with head and neck cutaneous malignancies reported a mean age of 32 years (range 10–43), with squamous cell carcinoma as the most common tumour type (6 patients) and the orbital region as the most common site (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). Five patients had local recurrences, and one was lost to follow-up. The authors state there is no definitive treatment algorithm and that early surgical intervention with close follow-up remains the standard.
A 2019 follow-up of two Japanese XP-A siblings with compound heterozygous mutations (IVS3-1G>C and c.682C>T, p.R228X) described a mild phenotype over 40 years, but provides no quantitative survival or response data. A 2023 Moroccan study describes the epidemiological, clinical, and histological profile of XP patients treated in a plastic surgery department in southern Morocco, but no drug intervention or outcome numbers are reported.
What is still missing: any controlled trial of a pharmacological agent for any XP complementation group, including the variant type; a validated biomarker or patient stratification method to predict which individuals might benefit from a given intervention; and dedicated funding for a prospective, multi-centre study that goes beyond surgical case series and descriptive epidemiology.
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.
AbstractBACKGROUND: Xeroderma pigmentosum is an extremely rare, autosomal recessive disease characterized by a more than 1000-fold increase in nonmelanoma skin cancer. Individuals with this disease can be divided into eight complementation groups: A-G and V for variant. Each one represents a different genetic defect in DNA repair. OBJECTIVE: To review the molecular basis of xeroderma pigmentosum. RESULTS: Deficiencies in various gene products in the nucleotide excision repair pathway cause xeroderma pigmentosum in complementation groups A-G. The molecular basis of the variant group remains to be elucidated. CONCLUSIONS: Research into the genetic defects underlying xeroderma pigmentosum have led to an increased understanding of nucleotide excision repair.
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.
JAAD Case Reports · 2019 · 3 citations · open access
Autopsy findings and clinical features of a mild-type xeroderma pigmentosum complementation group A siblings: 40 years of follow-up
AbstractXeroderma pigmentosum (XP) is an autosomal recessive disease characterized by abnormally accelerated photoaging skin symptoms for the patient's age caused by failure to repair DNA lesions damaged by ultraviolet radiation.1 Two sibling cases of Japanese XP-A patients display milder symptoms in those who harbor compound heterozygous mutation of IVS3-1G>C and c.682C>T, (p.R228X). We present a follow-up report on two patients, XP4KO and XP5KO, after a brief report from 25 years ago.2
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.
International Journal of Advanced 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.
