DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neurofibromatosis type 1 — screening already-approved drugs against its 25-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeurofibromatosis type 1 maps to a 25-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 neurofibromatosis type 1 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
FKBP prolyl isomerase 1A (FKBP1A) — FKBP1A 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 4~{s},5~{r},6~{z},9~{s},10~{s},12~{e}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I1S · 1.52 Å · ligand (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione (E26). Experimental structure, not a prediction.
What the evidence adds up to
Neurofibromatosis type 1 affects 1 in 3000 to 4000 people in the USA. The underlying pathogenesis has not been completely elucidated, and the disease is still associated with significant morbidity and mortality. Treatment options have historically been limited to surgery, with chemotherapy reserved for tumours that undergo malignant transformation. The MEK inhibitor selumetinib has received recent regulatory approvals for plexiform neurofibromas, reshaping the management landscape. However, there is still no agreed definition of plexiform neurofibroma, no standard diagnostic evaluation or surveillance strategy, and no clear indications for when to start treatment or which modality to select. A 2022 consensus panel of multidisciplinary NF1 experts addressed these questions but did not resolve them.
A 2017 case report describes a 66-year-old woman with NF1 who presented with painless progressive jaundice and was found at surgery to have three simultaneous abdominal tumours: a periampullary well-differentiated neuroendocrine tumour (carcinoid), a duodenal gastrointestinal stromal tumour, and a plexiform neurofibroma at the hepatic hilum. She underwent pancreatoduodenectomy and had no recurrence at two months. The authors conclude that NF1 patients with abdominal symptoms should be thoroughly evaluated to rule out multiple tumours.
A 2023 viewpoint notes that cutaneous manifestations of NF1 typically do not require intervention but emphasises that clinicians must be sensitive to the impact of the condition on quality of life. A 2025 perspective on gene therapy for NF1 states that approaches aimed at restoring neurofibromin quantity and function hold promise but are hindered by foundational gaps: the absence of quantitative assays, a lack of robust preclinical models with reliable functional readouts, and no clear path to overcoming these barriers. The Gilbert Family Foundation’s Gene Therapy Initiative has launched one of the first focused research efforts to support gene replacement, gene editing, and other strategies to upregulate neurofibromin, but the authors stress that addressing these challenges is critical before effective and durable gene therapy interventions can be realised.
What is still missing: a standardised definition and surveillance protocol for plexiform neurofibromas, clear treatment initiation criteria, quantitative assays for neurofibromin function, robust preclinical models with reliable readouts, and the funding and trial designs needed to translate gene therapy strategies from the laboratory into patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuro-Oncology · 2022 · 151 citations · open access
Management of neurofibromatosis type 1-associated plexiform neurofibromas
AbstractPlexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts.
Rare triad of periampullary carcinoid, duodenal gastrointestinal stromal tumor and plexiform neurofibroma at hepatic hilum in neurofibromatosis type 1: a case report
AbstractBACKGROUND: Neurofibromatosis type 1 is a relatively common inherited disorder. Patients with neurofibromatosis type 1 are at high risk of developing neurogenic, neuroendocrine and mesenchymal intra-abdominal tumors. Although coexistence of multiple tumors of different types is frequent in neurofibromatosis type 1, simultaneous occurrence of abdominal tumors of three types in very rare. CASE PRESENTATION: A 66-year-old lady with neurofibromatosis type 1 presented with painless progressive jaundice for six months. Laboratory investigations revealed iron deficiency anemia and conjugated hyperbilirubinemia. Tumor markers were normal. Abdominal computed tomography showed a 3 × 2 cm heterogenous mass in the periampullary region with mild dilation of the common bile duct and another 2 × 1.7 cm mass in the fourth portion of the duodenum. Endoscopic biopsy confirmed the diagnosis of periampullary carcinoid. At surgery, multiple small nodules were detected at the hepatic hilum. Frozen section suggested them to be neurofibromas. Patient underwent pancreatoduodenectomy and had uneventful recovery with no recurrence at two months. Microscopic examination of the resected specimen confirmed presence of three tumors: periampullary well differentiated neuroendocrine tumor, gastrointestinal stromal tumor of the fourth part of duodenum and plexiform neurofibroma at the hepatic hilum. CONCLUSION: Patients of neurofibromatosis type 1 with abdominal symptoms should be treated with high index of clinical suspicion and thoroughly evaluated to rule out multiple tumors.
Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors
AbstractNeurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2015 · 2 citations · open access
A Safe Alternative in Neurofibromatosis for Lower Limb Surgeries: Combined Femoral and Sciatic Nerve Block
AbstractNeurofibromatosis (NF) is a neurogenetic disease with multiple systemic involvement. In this case report we describe the successful management of a patient with NF posted for lower limb wound debridement with multiple neurofibromas over the back and face causing difficulty in spinal anesthesia and general anaesthesia. Combined femoral and sciatic nerve block was used as a safe alternative anaesthetic approach.
Clinical and Experimental Dermatology · 2023 · 1 citations
Living with neurofibromatosis
AbstractNeurofibromatosis type 1 is a genetic disorder that has a number of cutaneous manifestations. Although these lesions typically do not require any form of intervention, it is important for clinicians to be sensitive to the impact that this condition can have on patients’ quality of life regardless. This viewpoint highlights the difficulties encountered by our patient as a result of this condition.
Russian Journal of Pediatric Hematology and Oncology · 2021 · 1 citations · open access
The first experience of using MEK inhibitors for type 1 neurofibromatosis in children in the Russian Federation in a hospital for short-term treatment at the National Medical Research Center
AbstractNeurofibromatosis is a genetic disorder that affects the bones, soft tissues, skin, and the nervous system. Neurofibromatosis has been described in 1882, however, there is still no specific treatment for this disease and no treatment protocols for the most frequent and life-threatening complications such as non-malignant tumors deriving from the cells of the peripheral nerve sheaths. Progress in molecular genetic study discovered the underlying genetic alteration in this tumor. This knowledge provides the base for clinical trials with new drugs. MEK-inhibitors are acting on the RAS-MAPK signaling pathway and have shown their efficacy in decreasing the size of inoperable tumors in children with type 1 neurofibromatosis (NF1). Although, this therapy does not completely reduce the tumor volume, it can significantly improve the quality of life. This article presents a clinical case of the trametinib efficacy in a child suffering from NF1-associated plexiform neurofibromas.
Rare Disease and Orphan Drugs Journal · 2025 · 0 citations · open access
From hype to hope: foundational requirements for NF1 gene therapy success
AbstractGene therapy for Neurofibromatosis type 1 (NF1), defined as a collection of approaches that restore the quantity and function of neurofibromin, holds promise for treating various NF-associated clinical manifestations by addressing the root cause of the condition. The Gilbert Family Foundation’s Gene Therapy Initiative (GTI) launched one of the first focused research efforts to support a broad array of gene replacement, gene editing, and other strategies aimed at upregulating neurofibromin levels to mitigate symptoms and advance therapies for NF1. Efforts to discover and evaluate novel gene therapies to treat NF1 are hindered by foundational gaps in the field, the absence of quantitative assays, and a lack of robust preclinical models with reliable functional readouts. This perspective begins by shedding light on those key barriers that continue to hinder progress in NF1 gene therapy, outlines some of the strategies being explored to overcome them and offers pointers to additional strategies that merit further exploration. We then highlight several promising gene therapy strategies now in development. Successfully addressing the challenges described earlier is critical to realizing the full potential of these emerging and novel therapeutic approaches, setting the stage for effective and durable NF1 gene therapy interventions.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
TYPE 1 NEUROFIBROMATOSIS AND ANESTHESIA
AbstractType 1 Neurofibromatosis is a genetic disease that can vary in severity and affect different parts of the body, so anesthetists need to take this into account. Due to the various system involvements such as respiratory, central/peripheral nerve, musculoskeletal, cardiovascular, genitourinary, and gastrointestinal systems that Type- 1 neurofibromatosis may cause, anesthesia management should be carefully planned, and complications should be anticipated. Therefore, a detailed preoperative examination is necessary. Keywords: Neurofibromatosis,Spinal cord, Tumor.
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.
