DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Marshall-Smith syndrome — 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 moduleMarshall-Smith syndrome 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 marshall-smith 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
nuclear factor I X (NFIX) — NFIX 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9WA7 · 2.31 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Marshall-Smith syndrome is a rare congenital condition of unknown cause, with fewer than 50 patients described in the medical literature by 2010. An international collaboration using an online wiki presented 15 new patients, the oldest being 30 years, and updated four previously published cases. The main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behaviour, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features include a high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor brain morphology abnormalities such as hypoplasia of the corpus callosum are common. Array-CGH performed on 12 of the cohort found no copy number variants of clear clinical relevance.
Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. A 1997 report of a child diagnosed at 5 months described significant upper airway obstruction successfully treated, and aggressive management of failure to thrive allowed her to maintain weight on the 50th centile at 3.5 years. A 1999 report of a newborn male added cerebellar hypoplasia to the phenotypic spectrum, which had not been previously reported. A 1988 case in a 4-year-old girl found selective hypoplasia of type IIa and IIb muscle fibres, partial growth hormone deficiency, partial villous atrophy of the small bowel, and pronounced dicarboxylic aciduria; the significance of these findings was not clear.
Earlier reports emphasised that the prognosis has been poor, with death in early infancy common. A 1988 report stated that early evaluation of upper airway obstruction may be important in prolonging life, and that early recognition and aggressive multi-disciplinary therapy might permit further investigation. A 2002 case report from Korea, the first from that country, noted about 29 cases reported to date. What is still missing is any identified genetic cause, a systematic understanding of the metabolic and endocrine findings, and prospective data on whether early airway and feeding interventions reliably change long-term outcomes. No drug treatment has been studied in any of these reports.
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 Part A · 2010 · 55 citations · open access
Phenotype and natural history in Marshall–Smith syndrome
AbstractMarshall-Smith syndrome (MSS) is a distinctive entity of unknown etiology with fewer than 50 patients described in the medical literature to date. Through an International collaboration and use of an online wiki to facilitate data collection and sharing, we further delineate the phenotype and natural history of this syndrome. We present 15 new patients, the oldest being 30 years, provide an update on four previously published cases, and compare all patients with other patients reported in literature. Main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behavior, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features are characteristic with high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum are common. Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. Array-CGH was performed on 12 of the cohort and no copy number variants of clear clinical relevance were identified. The present study is the first reported use of an online wiki to aid delineation of a genetic syndrome, and illustrates its value in collecting detailed data in rare conditions.
Journal of Medical Genetics · 1997 · 23 citations · open access
Marshall-Smith syndrome: the expanding phenotype.
AbstractWe report a child of 3 years 9 months with the Marshall-Smith syndrome (MSS), characterised by the typical facial features, developmental delay, and advanced bone age. After the diagnosis was made at 5 months of age, careful observation for respiratory complications and failure to thrive was initiated. By 3 1/2 years of age, although our patient had no life threatening respiratory complications, investigation showed significant upper airway obstruction, which has been successfully treated. Aggressive treatment for failure to thrive has also allowed her to maintain a weight on the 50th centile. The purpose of this report is to suggest that early diagnosis and aggressive management may improve the ultimate prognosis with respect to the respiratory and feeding difficulties seen in this rare syndrome.
Clinical Dysmorphology · 1999 · 22 citations · open access
Marshall-Smith syndrome
AbstractMarshall-Smith syndrome is a rare congenital condition, characterized by advanced bone age, facial anomalies and relative failure to thrive. We report a newborn male with Marshall-Smith syndrome and summarize 21 previously reported cases. We report cerebellar hypoplasia in our patient, which has not been previously reported in subjects with this rare syndrome. This patient's findings broaden the phenotypic spectrum seen in Marshall-Smith syndrome.
AbstractA 4-year-old girl with the Marshall-Smith syndrome (MSS) is described. A muscle biopsy was performed because of hypotonia and muscular weakness. Selective hypoplasia of type IIa and IIb fibers was found. Additional not previously reported findings in this girl were a partial growth hormone deficiency, a partial villous atrophy of the small bowel and a pronounced dicarboxylic aciduria. The significance of these findings in MSS is not clear and the results of similar investigations in other MSS patients have to be awaited.
AbstractWe have reported a case of the Marshall-Smith syndrome, a condition characterized by accelerated bone maturation, dysmorphic features, respiratory compromise, failure to thrive, neuro-developmental abnormalities, and death in early infancy. Early evaluation of upper airway obstruction in these children may be important in prolonging life. Although the prognosis has been poor to date, early recognition and aggressive multi-disciplinary therapy may permit further investigation into the cause and appropriate management of this disorder.
Journal of the Korean Radiological Society · 2002 · 0 citations
Marshall-Smith Syndrome: Case Report
AbstractMarshall-Smith syndrome is a rare disease, with about 29 cases reported to date. It is characterized by accelerated bony growth and maturation, phalangeal abnormalities (wide middle and narrow distal phalanges), unusual facial features (prominent eyes, bluish sclerae, coarse eyebrows, an upturned nose, hypoplastic facial bones, and shallow orbits), failure to thrive, respiratory difficulties, and psychomotor retardation. This report of the radiologic findings of Marshall-Smith syndrome is, as for as we know, the first to be published in Korea.
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.
