DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for xeroderma pigmentosum — screening already-approved drugs against its 11-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 maps to a 11-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 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…
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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
Xeroderma pigmentosum is an autosomal recessive disease with a 1000-fold increased risk of cutaneous neoplasms. A narrative review from 2022 states there is no cure. Management centres on rigorous sun avoidance and protection. For existing skin cancers, options include photodynamic therapy, curettage and electrodesiccation, or surgical excision. Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil are used for prevention of skin malignancy. Poikiloderma can be treated with chemical peeling, dermabrasion or laser resurfacing. Methylcellulose eyedrops and soft ultraviolet-protective contact lenses may keep the cornea moist. Investigational therapies mentioned in that review are T4 endonuclease-V liposome lotion and oral nicotinamide to reduce actinic keratoses and non-melanoma skin cancers, and gene therapy.
A 2003 case report describes a 19-year-old woman with XP who had an excellent clinical response of multiple small pigmented basal cell carcinomas and pigmentary changes using imiquimod 5% cream, with only minor side-effects. A 2016 surgical series of 11 XP patients with head and neck cutaneous malignancies reported a mean age of 32 years (range 10–43). The most common tumour type was squamous cell carcinoma (6 patients), and the most common location was the orbital region (4 patients). Free tissue transfer was the most common surgical intervention (4 patients). The average number of surgical procedures was 5.5 (range 1–25). Five patients had local recurrences, and one patient was lost to follow-up. The authors note no definitive treatment algorithm and state that early surgical intervention and close follow-up are the gold standard because of rapid tumour growth and possible recurrence.
A 2018 review notes that development of therapeutic strategies has trailed behind mechanistic discoveries. It reports that specific sulfonylureas promote clearance of DNA damage and increase resistance to ultraviolet radiation in a cellular model of XP. Nicotinamide attenuates the effects of ultraviolet radiation in cells, and caloric restriction decreases DNA damage burden in animal models. The review concludes that clinical management still focuses on preventative avoidance of sun exposure rather than therapies that improve the patient’s condition. Two 2023 abstracts from southern Morocco describe XP as relatively frequent in countries with high consanguinity rates, but provide no new efficacy data.
What is still missing is a definitive treatment algorithm, any therapy that reverses the underlying DNA repair defect, and large-scale clinical trials that test the candidate agents (sulfonylureas, nicotinamide, caloric restriction) in patients rather than in cells or animal models. Patient stratification by XP complementation group and neurological involvement is not addressed in the available trial data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Drugs in Context · 2022 · 71 citations · open access
Xeroderma pigmentosum: an updated review
AbstractBackground: Early recognition of xeroderma pigmentosum is important to minimize the complications arising from the harmful effects of exposure to ultraviolet radiation. This narrative review aims to familiarize physicians with the clinical features, diagnosis and management of xeroderma pigmentosum. Methods: A search was conducted in December 2021 in PubMed Clinical Queries using the key term "xeroderma pigmentosum". The search strategy included all clinical trials, observational studies and reviews published within the past 10 years. The information retrieved from the search was used in the compilation of this article. Results: laser resurfacing, fractional/pulsed laser therapy, and photodynamic therapy. Cutaneous malignancy can be treated by photodynamic therapy, curettage and electrodesiccation, or surgical excision. Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil can be used for the prevention of skin malignancy. Treatment options for poikiloderma include chemical peeling, dermabrasion and laser resurfacing. Methylcellulose eyedrops and soft ultraviolet-protective contact lenses may be used to keep the cornea moist and protect against the harmful effects of keratitis sicca. Investigational therapies include the use of T4 endonuclease-V liposome lotion and oral nicotinamide to reduce the rate of actinic keratoses and non-melanoma skin cancers and gene therapy for radical cure of this condition. Conclusion: Although currently there is no cure for xeroderma pigmentosum, increased awareness and early diagnosis of the condition, followed by rigorous sun avoidance and protection and optimal management, can dramatically improve the quality of life and life expectancy.
British Journal of Dermatology · 2003 · 38 citations
Excellent response of basal cell carcinomas and pigmentary changes in xeroderma pigmentosum to imiquimod 5% cream
AbstractXeroderma pigmentosum (XP) is an autosomal recessive disease in which patients have a 1000-fold increased risk of developing cutaneous neoplasms. Management of patients with XP is a difficult therapeutic challenge as they usually present with many cutaneous malignancies and continue to form skin tumours at a high rate. We describe a 19-year-old woman with XP who had been previously treated with many different therapeutic approaches. She had an excellent clinical response of her multiple small pigmented basal cell carcinomas and pigmentary changes using imiquimod 5% cream with only minor side-effects.
British Journal of Dermatology · 2018 · 25 citations
Novel therapeutic approaches to xeroderma pigmentosum
AbstractBACKGROUND: The study of xeroderma pigmentosum has yielded unforeseen advances regarding how defects in the nucleotide excision repair pathway result in this devastating disease, but development of therapeutic strategies has trailed behind the mechanistic discoveries. OBJECTIVES: This review aims to cover clinical presentation, molecular mechanisms and current management, and highlights more recent insights into targeting the deficiencies secondary to the DNA repair defects to prevent skin cancer and/or neurological degeneration. METHODS: This review article discusses novel therapeutic approaches to xeroderma pigmentosum that focus on metabolic defects downstream of nucleotide excision repair. RESULTS: Current research demonstrates that specific sulfonylureas promote clearance of DNA damage and increase resistance to ultraviolet radiation in a cellular model of xeroderma pigmentosum. Moreover, nicotinamide attenuates the effects of ultraviolet radiation in cells, and caloric restriction decreases DNA damage burden in animal models of xeroderma pigmentosum. CONCLUSIONS: Clinical management of patients with xeroderma pigmentosum still focuses on preventative avoidance of sun exposure as opposed to therapies that would improve the patients' condition; thus, novel approaches to this disease are warranted.
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.
AbstractJournal Article The challenge of xeroderma pigmentosum Get access António Gentil Martins António Gentil Martins Surgeon in Charge Paediatric Department, Institu'To Portugués De Oncologia, Lisboa, Portugal Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 52, Issue 7, July 1965, Pages 526–530, https://doi.org/10.1002/bjs.1800520711 Published: 08 December 2005
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.
