DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for large congenital melanocytic nevus — 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 moduleLarge congenital melanocytic nevus 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 large congenital melanocytic nevus 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Ten patients with giant congenital melanocytic nevi that could not be closed by primary closure received a treatment that combined an inactivated autologous nevus with a cultured epidermal autograft. The full-thickness nevus was removed, pressurised at 200 MPa for 10 minutes to inactivate it, then sutured back to the original site. Four weeks later a cultured epidermal autograft was applied. One patient dropped out. At 52 weeks, no recurrence of nevus was detected by pathological diagnosis in any of the nine remaining patients. The L* value (skin lightness) at 52 weeks was significantly higher than that of the original target nevus. The epithelised area of the reconstructed skin, expressed as a percentage of the original target nevus, was 55.5 ± 19.4 percent at 12 weeks and 85.0 ± 32.4 percent at 52 weeks. One patient required skin grafting because of contracture of the reconstructed skin. The authors note that the inactivated nevus caused inflammation and contracture for several months.
A separate case report describes surgical management of a giant congenital melanocytic nevus in a school-aged child using dermal substitutes and skin grafts, with subjective improvement in quality of life. Another case report presents a term male neonate with a giant congenital melanocytic nevus in a torso mosaic pattern, confirming the diagnosis by the presence of pigmented rough skin, wart-shaped lesions, and demarcated borders. That report states the condition has a prevalence of 1 per 20,000 live births and is caused by intrauterine somatic mutations in genes of the mitogen-activated protein kinase pathway. It notes that the lesion may associate with severe complications such as malignant melanoma, and that there is no consensus in the literature about the greater benefit of surgical versus nonsurgical management.
What is still missing is a larger sample size to confirm the safety and efficacy of the high-hydrostatic-pressure inactivation and autograft combination, longer follow-up beyond 52 weeks to assess malignant transformation risk, and a controlled comparison with standard surgical excision or other treatments. The trial was first-in-human and open-label, with no blinding or randomisation. Patient stratification by nevus size, location, and age at treatment has not been established.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PEDIATRICS · 2019 · 59 citations
Giant Congenital Melanocytic Nevus Treated With Trametinib
AbstractGiant congenital nevi are melanocytic proliferations of the skin that may be complicated by melanoma, neurocutaneous melanocytosis, pain, pruritus, and disfigurement. Current treatment options include surgical resection and medical management of associated symptoms. There is limited efficacy in these modalities. No effective pharmacologic treatments are available for the treatment of these lesions. We present the case of a 7-year-old girl with a giant congenital melanocytic nevus that had an AKAP9-BRAF fusion and was treated with trametinib, which resulted in rapid resolution of the patient’s lifelong, intractable pain and pruritus as well as dramatic improvement in the extent of her nevus.
Plastic & Reconstructive Surgery · 2021 · 5 citations
A Novel Treatment for Giant Congenital Melanocytic Nevi Combining Inactivated Autologous Nevus Tissue by High Hydrostatic Pressure and a Cultured Epidermal Autograft: First-in-Human, Open, Prospective Clinical Trial
AbstractBACKGROUND: Giant congenital melanocytic nevi are large skin lesions associated with a risk of malignant transformation. The authors developed a novel treatment to reconstruct full-thickness skin defects by combining an inactivated nevus as the autologous dermis and a cultured epidermal autograft. The first-in-human trial of this treatment was performed. METHODS: Patients with melanocytic nevi that were not expected to be closed by primary closure were recruited. The full-thickness nevus of the target was removed and inactivated by high hydrostatic pressurization at 200 MPa for 10 minutes. The inactivated nevus was sutured to the original site, and a cultured epidermal autograft was grafted onto it 4 weeks later. Patients were followed for up to 52 weeks. RESULTS: Ten patients underwent reimplantation of the pressurized nevus, and one patient dropped out. The recurrence of nevus at 52 weeks was not detected by pathological diagnosis in any patients. The L* value at 52 weeks was significantly higher than that of the target nevus. One patient received skin grafting due to contracture of the reconstructed skin. The epithelized area of the reconstructed skin, as the percentage of the original target nevus, was 55.5 ± 19.4 percent at 12 weeks and 85.0 ± 32.4 percent at 52 weeks. CONCLUSIONS: The inactivated nevus caused inflammation and contracture for several months. However, no recurrence was observed, and combination therapy using an inactivated nevus with a cultured epidermal autograft may therefore be a novel treatment of giant congenital melanocytic nevi. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Plastic & Reconstructive Surgery Global Open · 2021 · 2 citations · open access
Giant Congenital Melanocytic Nevus in a Pediatric Patient: Case Report
AbstractThe giant congenital melanocytic nevus is a rare entity with an extremely low incidence that appears at the time of birth and generally involves the dermis but may also affect other skin layers. According to its clinical evolution, the probability of malignancy may vary, so proper follow-up is essential for potential management. There is no consensus in the literature about the greater benefit of surgical versus nonsurgical management. In this case report, we present the surgical management of a school-aged patient using dermal substitutes and skin grafts, subjectively obtaining an improvement in his quality of life.
مجله پزشکی بالینی ابن سینا · 2021 · 1 citations · open access
A Case Report of Giant Congenital Melanocytic Nevus
AbstractBackground: Giant congenital melanocytic nevus is caused by intrauterine somatic mutations in the genes involved in the mitogen-activated protein kinase pathway. It is a rare melanocytic lesion with a prevalence of 1 per 20,000 live births occurring at birth or shortly thereafter. Case Presentation: Here, we presented the case of a term male neonate with giant congenital melanocytic nevus. He was born to a 33-year-old mother. The initial pediatric examination revealed a skin mosaic pattern in his torso. The pigmented and rough skin of this area, along with several prominent wart-shaped lesions and demarcated borders, confirmed the giant congenital melanocytic nevus. Conclusion: Despite the rarity of this lesion, it is of great importance since it may associate with severe complications, such as malignant melanoma. Therefore, it is necessary to adopt appropriate medical management by recognizing the nature of the lesion.
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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