DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Noonan syndrome 13 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNoonan syndrome 13 maps to a 1-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 noonan syndrome 13 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
mitogen-activated protein kinase 1 (MAPK1) — MAPK1 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 2~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AOJ · 1.12 Å · ligand 1-[(2~{S})-2-(5-methyl-3-pyridin-4-yl-1~{H}-pyrazol-4-yl)pyrrolidin-1-yl]propan-1-one (N8L). Experimental structure, not a prediction.
What the evidence adds up to
Noonan syndrome is a genetic disorder affecting 1 in 1000 to 2500 children, characterised by short stature, cardiovascular abnormalities, characteristic facies, learning difficulties, developmental delay, bleeding manifestations, and lymphatic malformation. Most individuals with the condition live a normal life. The syndrome is caused by mutations in genes of the RAS/MAPK-signaling cascade, including PTPN11, KRAS, SOS1, and RAF1, but overall mutations are identified in only about 70% of patients. In two siblings with Noonan syndrome who had no mutations in PTPN11, KRAS, SOS1, or RAF1, a balanced rearrangement of chromosome 12 was found, inherited from a phenotypically normal mother who had mosaicism for the derivative chromosome. Microarray analysis showed no gains or losses near the breakpoints, and neither the PTPN11 nor KRAS region was involved, suggesting other candidate genes on chromosome 12 may cause the phenotype.
Audiological assessment of a five-year-old boy with Noonan syndrome who could only produce a few meaningful words showed bilateral mild conductive hearing loss at low frequencies. Auditory brainstem response recordings showed good waveform morphology but atypical results: absolute latency of wave V was normal, interpeak latencies of waves I-V, I-II, and II-III were prolonged, while interpeak latency of waves III-V was abnormally shorter. As of 2018, no publication had used auditory electrophysiological tests to analyse the central auditory nervous system in Noonan syndrome patients.
A case report of a twenty-six-month-old boy diagnosed with Noonan syndrome attributed the condition to sporadic inheritance secondary to advanced paternal age. The report stated that a multidisciplinary approach is key to managing children diagnosed at an early age. No drug treatment or clinical trial data appear in any of these abstracts. What remains missing is identification of the remaining causative genes, systematic audiological evaluation protocols for the syndrome, and any interventional trial design or patient stratification that could test a therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Postgraduate Medical Journal · 1987 · 13 citations · open access
Colobomata associated with Noonan’s syndrome
AbstractA patient with Noonan's syndrome and fundal colobomata in both eyes is described. To our knowledge, this is the first report of the association of colobomata with Noonan's syndrome. Although the patient had poor sight since early childhood and dyspnea on exertion as a teenager, the diagnosis of Noonan's syndrome was not made until early adulthood. We hope this report will encourage recognition of this syndrome and its implications at an earlier stage.
American Journal of Medical Genetics Part A · 2009 · 8 citations · open access
Molecular characterization of a balanced rearrangement of chromosome 12 in two siblings with Noonan syndrome
AbstractThe etiology of Noonan syndrome (NS) has been greatly elucidated with the discovery of the disease causative genes PTPN11, KRAS, SOS1, and RAF1, all involved in the RAS/MAPK-signaling cascade. Given that overall mutations are identified in about 70% of patients, identification of other NS associated genes remains a high priority to fully understand the etiopathogenesis of the condition. We report two affected siblings with an apparently balanced rearrangement of chromosome 12 ins(12)(q12p11.2p12.3) which segregates with the Noonan phenotype. The rearrangement was inherited from the phenotypically normal mother who had mosaicism for the derivative chromosome 12. There were no mutations of PTPN11, KRAS, SOS1, or RAF1 genes detected in the probands. Using fluorescence in situ hybridization analysis we identified the three breakpoints involved at 12p12.3, 12p11.2, and 12q12. By microarray analysis, there were no gains or losses near the breakpoints. Neither, the PTPN11 or KRAS region on chromosome 12 was involved in the rearrangement. We hypothesize that other NS candidate gene(s) may be located in the breakpoint regions of chromosome 12 causing the Noonan phenotype in both of these children.
AbstractNoonan syndrome is a relatively common dysmorphic syndrome. The typical features include short stature, cardiovascular abnormalities and a characteristic facies. Children with Noonan syndrome have a considerable number of potential health problems, which are highlighted in this article. However, most individuals with this condition live a normal life.
Frontiers in Endocrinology · 2024 · 5 citations · open access
Gonadal dysfunction in a man with Noonan syndrome from the LZTR1 variant: case report and review of literature
AbstractNoonan syndrome (NS) is a genetic disorder characterized by multiple congenital defects caused by mutations in the RAS/mitogen-activated protein kinase pathway. Male fertility has been reported to be impaired in NS, but only a few studies have focused on fertility status in NS patients and underlying mechanisms are still incompletely understood. We describe the case of a 35-year-old man who underwent an andrological evaluation due to erectile dysfunction and severe oligospermia. A syndromic facial appearance and reduced testis size were present on clinical examination. Hormonal evaluation showed normal total testosterone level, high FSH level, and low–normal AMH and inhibin B, compatible with primary Sertoli cell dysfunction. Genetic analysis demonstrated the pathogenetic heterozygous variant c.742G>A, p.(Gly248Arg) of the LZTR1 gene (NM_006767.3). This case report provides increased knowledge on primary gonadal dysfunction in men with NS and enriches the clinical spectrum of NS from a rare variant in the novel gene LZTR1 .
Function and Disability Journal · 2018 · 0 citations · open access
The Results of ABR in a Child with Noonan Syndrome: Necessity of Renewing the Evaluation Protocols of Syndromes
Abstract55 years after discovering NS, there was not even one publication regarding the use of auditory electrophysiological tests for analyzing the central auditory nervous system in NS patients. This is an attempt to attract attention of scientists and clinicians in using AEPs for evaluating the function of CANS in NS. Readers can find a report about the results of audiological tests and auditory brainstem response (ABR) findings in a 5-year old Malay boy with NS. It should be noted that he could only produce a few meaningful words. The results of audiological tests showed bilateral mild conductive hearing loss at low frequencies. ABR recordings showed good waveform morphology but the results were atypical. That is, absolute latency of wave V was normal but interpeak latencies of waves I-V, I-II, II-III were prolonged. Conversely, interpeak latency of waves III-V was abnormally shorter.
Journal of Evolution of Medical and Dental Sciences · 2015 · 0 citations · open access
NOONAN SYNDROME: AN EARLY DIAGNOSIS
AbstractNoonan syndrome is a genetic multisystem disorder characterised by facial dysmorphism, learning difficulties, developmental delay, short stature, cardiac defects, bleeding manifestations and lymphatic malformation affecting 1 in 1000-2500 children. This is a case report of a twenty six month old boy diagnosed to have Noonan syndrome with sporadic inheritance secondary to advanced paternal age. Multidisciplinary approach is the key to success in managing these children, who are diagnosed at an early age.
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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