DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for xeroderma pigmentosum group D — 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 moduleXeroderma pigmentosum group D 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 xeroderma pigmentosum group d 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 2, TFIIH core complex helicase subunit (ERCC2) — ERCC2 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 28JM · 3.29 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 from a 1994 study, 25 (86%) carried a homozygous splicing mutation at intron 3 of the XPA gene. Those patients developed 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 that splicing mutation; at least three of them had milder skin and neurologic symptoms. Two patients (single-ovum 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 may produce different clinical features.
A 2016 case series from a single centre reported 11 xeroderma pigmentosum patients with head and neck cutaneous malignancies treated between 2005 and 2015. Mean age was 32 years (range 10–43); 4 were male, 7 female. The most common tumour was squamous cell carcinoma (6 patients), and the most common location was the orbital region (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, 5 had local recurrences, and one was lost to follow-up. The authors stated there is no definitive treatment algorithm and that early surgical intervention with close follow-up remains the gold standard because of rapid tumour growth and recurrence risk.
A 1995 report described a 12-year-old boy diagnosed with group D xeroderma pigmentosum by unscheduled DNA synthesis and complementation tests. He had more than 200 moles distributed over his entire body, including unexposed areas of torso and scalp. All eight removed specimens were histologically compatible with nevocellular nevi.
No controlled trial has tested any systemic therapy for xeroderma pigmentosum group D. The genetic basis of the group A form is partly characterised, but for group D the molecular details and their correlation with clinical severity remain poorly defined. What is missing is a sufficiently large, genetically stratified cohort to link specific XPD mutations to disease progression, and a trial design that can test whether early surgical surveillance or any systemic intervention alters long-term outcomes. Funding for such natural history studies and for any drug-repurposing screen in patient-derived cells 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.
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.
Indian Journal of Dermatology Venereology and Leprology · 2021 · 13 citations · open access
Therapeutics of xeroderma pigmentosum: A PRISMA-compliant systematic review
AbstractXeroderma pigmentosum is a rare hereditary autosomal recessive genodermatosis. At present, there are many treatment options for xeroderma pigmentosum, covering medical/procedural, surgical and combined modalities. However, the quality of these interventions has not been assessed. Our study aimed to perform a systematic review of the literature regarding the treatment of xeroderma pigmentosum. Multiple medical databases were accessed with the Medical Subject Headings terms; "xeroderma pigmentosum," "therapeutics" and "surgical procedures, operative" from January 2000 to April 2019, including articles published in Portuguese, Spanish and English (PROSPERO-CRD42018114858). Two hundred and ninety-eight studies were found in the databases researched, of which, after applying the inclusion criteria, only 33 studies remained. The 33 complete articles were read by three of the authors, having been found: 16 reported medical/procedural and 17 reported surgical treatments. Only one clinical study presented a good level of evidence (EL: 2): a randomized clinical trial using a T4 endonuclease V (T4N5) liposome lotion which reduced the development of skin lesions in patients with xeroderma pigmentosum. Amongst surgical modalities, all studies presented low evidence level (EL: 4). Three illustrative cases are also presented, to emphasize the multiple number of times that surgical modalities may be required in these patients. The therapeutic modalities, both clinical and surgical, for xeroderma pigmentosum presented a low level of scientific evidence which did not allow meta-analysis. More therapeutic studies, both clinical and surgical, with better scientific evidence are needed.
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.
Group D Xeroderma Pigmentosum: A Case with a Number of Nevocellular Nevi
AbstractA 12-year-old boy was diagnosed as having group D xeroderma pigmentosum based on the results of unscheduled DNA synthesis (UDS) tests and complementation tests. More than 200 moles were distributed all over his body, including the unexposed areas of his torso and scalp. All of eight removed specimens were compatible histologically with nevocellular nevi.
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.
