DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Hurler-Scheie syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHurler-Scheie syndrome maps to a 2-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 hurler-scheie 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
alpha-L-iduronidase (IDUA) — IDUA 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 1~{r},2~{r},3~{r},4~{s},6~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I6R · 2.02 Å · ligand (1~{R},2~{R},3~{R},4~{S},6~{S})-6-azanyl-2,3,4-tris(oxidanyl)cyclohexane-1-carboxylic acid (H62). Experimental structure, not a prediction.
What the evidence adds up to
In a 2017 retrospective review of 55 patients with Hurler syndrome, 98% showed signs of disease during the first six months of life. Early manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference appeared at a median age of 8–10 months. Gross motor development was the most severely affected area during the first 12 months, and many patients had language delays, but cognition was typically preserved in that period. The authors note that no reliable prognostic biomarker exists to distinguish Hurler syndrome from the attenuated phenotypes (Hurler-Scheie and Scheie syndromes) in newborn screening, complicating treatment decisions.
A 1952 description characterises Hurler’s disease by mental defect, chondro-osteodystrophy, hepatosplenomegaly, and corneal opacities. A 2014 case report of a five-year-old girl with Scheie syndrome (the least severe form) describes disproportionate short stature, protuberant abdomen, mild proptosis, enlarged skull, prominent forehead, low-set ears, simian crease, clawed hand, mild kyphosis, strabismus, normal IQ, and hepatomegaly. Diagnosis was confirmed by deficient alpha-L-iduronidase enzyme activity in fibroblasts. The report states that management is multidisciplinary and includes physiotherapy, bone marrow or umbilical cord blood transplant to preserve neurocognition and improve somatic disease, and enzyme replacement therapy to slow disease progression.
A separate 2014 report describes a female patient with Hurler-Scheie syndrome who had undergone haematopoietic cell transplantation and presented with growth retardation and delayed puberty. She started growth hormone treatment at age 12.33 years, and the authors report significantly improved linear growth and predicted adult height. No controlled trial data are provided.
What is still missing is a reliable biomarker to predict central nervous system involvement in newborns with MPS I, which would allow clinicians to choose between haematopoietic cell transplant and enzyme replacement therapy. Prospective studies with standardised outcome measures are lacking, and no randomised trial has tested growth hormone in this population. Patient stratification by genotype and residual enzyme activity remains an unresolved need.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Orphanet Journal of Rare Diseases · 2017 · 74 citations · open access
Early disease progression of Hurler syndrome
AbstractBACKGROUND: Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler-Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. RESULTS: Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child's medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8-10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved during this period. CONCLUSIONS: In this large cohort of patients with Hurler syndrome, the vast majority showed signs and symptoms of disease during the first months of life. More research is needed to determine the extent to which early clinical manifestations of MPS I can predict phenotype and treatment outcomes.
AbstractHurler's disease is a condition characterized essentially by mental defect, chondro-osteodystrophy, hepatosplenomegaly and corneal opacities. The complex was first noted in 1900, by John Thomson of Edinburgh who, recognizing that he was dealing with a new disease, named it after his first patient “Johnny McL—'s Disease.” Subsequent descriptions were those of Hunter (1917) and Gertrud Hurler (1919).
Journal of Pediatric Endocrinology and Metabolism · 2014 · 7 citations
Growth hormone treatment in a patient with Hurler-Scheie syndrome
AbstractA female patient with known Hurler-Scheie syndrome, who underwent hematopoietic cell transplantation, presented with growth retardation and delayed puberty. She started growth hormone (GH) treatment at age 12.33 years, resulting in significantly improved linear growth and predicted adult height. We describe details of her clinical course and literature review of growth pattern as well as GH use in patients with mucopolysaccharidosis I.
Archives of Disease in Childhood · 2014 · 0 citations · open access
PO-0091 5 Year Old Girl With Disproportionate Short Stature With Failure To Thrive And Dysmorphism: Rare Case Of Scheie Syndrome
Abstract<h3>Background</h3> Hurler-Scheie Syndrome is an autosomal recessive mucopolysaccharidois resulting in reduced activity of α-L-iduronidase with accumulation of heparin and dermatan sulphate. Scheie syndrome represents less severely affected form with varied clinical features. <h3>Case Report</h3> 5 year female, first born child of 2nd degree consanguineous Egyptian parents, referred for short stature presented with following features. On examination: Length: 88 cm; Upper: Lower segment=1:1.3; weight: 12.3 kg; Head circumference: 51 cm Protuberant abdomen, mild proptosis, enlarged skull, prominent forehead, low set ears, simian crease, clawed hand, mild kyphosis, strabismus, normal IQ, hepatomegaly. Investigation: USG: hepatomegaly, Karyotyping normal Mild delay bone age; Elevated TSH, low T4; tissue transglutaminase normal; sweat chloride test normal; ammonia, lactate normal; growth hormone assay normal; Deficient enzyme in fibroblast confirmed diagnosis of Scheie syndrome <h3>Discussion</h3> Scheie syndrome is an autosomal recessive, rare lysosomal storage disease, with skeletal deformities and motor delay; described first in 1972; caused by mutations in <i>IDUA</i> gene (4p16.3) leading to partial deficiency in alpha-L-iduronidase enzyme and lysosomal accumulation of dermatan and heparan sulfate. Genetic testing is available. Antenatal diagnosis done by measurement of enzymatic activity in chorionic villus/ amniocytes and by genetic testing (if disease-causing mutation is known). Genetic counselling is recommended. Management is multidisciplinary including physiotherapy (to maintain range of movement); bone marrow or umbilical cord blood transplant (to preserve neurocognition, improve somatic disease and increase survival). Enzyme replacement therapy slows disease progression. <h3>Conclusion</h3> Scheie syndrome should be considered in differential diagnosis of disproportionate short stature with dysmorphism, failure to thrive with normal IQ.
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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