DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neurofibromatosis-Noonan syndrome — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeurofibromatosis-Noonan syndrome maps to a 7-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-noonan syndrome 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
A four-generation family in which neurofibromatosis type 1 and Noonan syndrome appeared together was found to carry a nonsense mutation (C2446T→R816X) in the neurofibromin gene. The mutation created a recognition site for endonuclease HphI that was absent in two family members who had Noonan syndrome only. Screening 184 unrelated NF1 patients turned up three further occurrences of the same mutation, all in individuals diagnosed with classical NF1. The authors concluded that the neurofibromatosis-Noonan phenotype in that family was additive, the result of both classical NF1 and Noonan syndrome, and they suggested the presence of a Noonan syndrome locus on chromosome 17q.
A later report described a different family with an unusual NF1 mutation and variable features of both NF1 and Noonan syndrome. The authors hypothesised that an NF1 mutant allele can itself produce diagnostic manifestations of Noonan syndrome, supporting the idea that allelic heterogeneity at the NF1 locus causes the combined phenotype. A 2011 case report of a 17-year-old boy with NF1 and Noonan-like features who developed progressive blue-grey lesions on his back noted that the phenotypic overlap can be explained by the involvement of the RAS-MAPK pathway in both disorders.
No treatment data appear in any of these abstracts. No drug is mentioned. The reports are limited to genetic characterisation and clinical description of small numbers of families and single cases. What is missing is any prospective trial, any drug intervention, any systematic patient stratification beyond mutation screening, and any funding for a treatment study in this rare combined phenotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 1985 · 123 citations
Noonan phenotype associated with neurofibromatosis
AbstractWe report on four patients with neurofibromatosis and manifestations of Noonan syndrome including short stature, ptosis, "midface hypoplasia," apparently short webbed neck, learning disabilities, and weakness. No family history of neurofibromatosis was present in any case. Average paternal and maternal age at birth was 37 and 28 years, respectively, suggestive of a new mutation. The presence of a distinct phenotype and hypotonia in these patients with neurofibromatosis is suggestive of a new separate disorder.
American Journal of Medical Genetics · 1998 · 44 citations
Novel recurrent nonsense mutation causing neurofibromatosis type 1 (NF1) in a family segregating both NF1 and Noonan syndrome
AbstractNeurofibromatosis type 1 (NF1), a genetic disorder with neuroectodermal involvement, demonstrates phenotypic overlap in some patients with Noonan syndrome (NS), ultimately resulting in the so-called neurofibromatosis-Noonan syndrome (NF-NS). A strong association of the two phenotypic traits was recently illustrated by a four-generation family, although NF1 and NS were eventually demonstrated to segregate independently on the basis of polymorphic DNA markers [Bahuau et al., 1996: Am J Med Genet 66:347-355]. Identification of the causal NF1 mutation seemed a prerequisite to further dissecting this singular familial association. Using the protein truncation assay, a nonsense mutation (C2446T-->R816X) of the neurofibromin gene was evidenced. This mutation occurred on a CpG dinucleotide within exon 16 and 5' to the GAP domain-specifying region of the gene. R816X creates a recognition site for endonuclease HphI, absent in 2 individuals with NS only. Screening 184 unrelated NF1 patients, three novel occurrences of the mutation were found in individuals diagnosed with classical NF1. Based on the assumption of genotype-phenotype correlation in these individuals, clinical and molecular analyses of this four-generation family demonstrated that the NF-NS phenotype was additive, being the result of both classical NF1 and NS. This particular observation also suggests the presence of an NS locus on 17q, which might be of interest for further linkage studies.
Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype
AbstractNeurofibromatosis-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndrome, which are separate syndromes. Potential etiologies of NFNS include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS.
Neurofibromatosis-Noonan syndrome: Case report and clinicopathogenic review of the Neurofibromatosis-Noonan syndrome and RAS-MAPK pathway
AbstractNeurofibromatosis-Noonan syndrome is an entity that combines both features of Noonan syndrome and Neurofibromatosis type 1. This phenotypic overlap can be explained by the involvement of the RAS-MAPK pathway (mitogen-activated protein kinase) in both disorders. We report the case of a 17-year-old boy with Neurofibromatosis 1 with Noonan-like features, who complained of the progressive appearance of blue-gray lesions on his back.
Pediatric Dermatology · 2024 · 2 citations · open access
Noonan syndrome‐like disorder: Case report and review of the literature
AbstractOf patients with a Noonan syndrome phenotype, only about 1% are found to be related to pathological variants in CBL, also known as Noonan syndrome-like disorder (NSLD). We present a case of a 4-year-old boy diagnosed with NSLD, presenting with multiple melanocytic nevi and superficial neurofibromas. A literature review identified common cutaneous findings of NSLD, for example, café-au-lait macules (22%), juvenile xanthogranuloma (16%), and thin hair (10%). As there are no documented cases of neurofibromas associated with NSLD, and only a single report of multiple melanocytic nevi, inclusion of these features in the phenotype may be warranted and mitigate the necessity for future biopsies in other children.
Neurofibromatosis-Noonan Syndrome Due to a Newly Occurred Microdeletion 17q11.2
AbstractBackground: Noonan syndrome (NS; 1: 500–2,500 births) and neurofibromatosis type 1 (NF1; 1: 3,000) are among the most common genetic diseases. They belong to the neuro-cardio-facio-cutaneous syndromes, which are accompanied by an over-function of the RAS-MAPK pathway (so-called RASopathies). RAS is involved in the induction of unhindered cell growth, disturbance of apoptosis, cell invasivity, and neoangiogenesis. We describe a boy with clinical symptoms of NF1 and NS.
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.
