DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for de Barsy 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 moduleDe Barsy 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 de barsy 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
aldehyde dehydrogenase 18 family member A1 (ALDH18A1) — ALDH18A1 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 2H5G · 2.25 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
De Barsy syndrome is a rare autosomal recessive genetic disorder characterised by severe cutis laxa, joint hypermobility, growth retardation, intellectual disability, and characteristic facies. Orthopaedic manifestations include developmental dysplasia of the hip, scoliosis, multiple joint dislocations and subluxations, and congenital vertical talus. The management of these orthopaedic problems has been described in two typical cases from 1994. A 2009 Italian case report stated that clinical, phenotypic, and structural data confirmed the elastic component is mostly affected, and ultrastructural and immunochemical findings suggested both elastic fibre degradative and synthetic processes are involved.
Some cases of de Barsy syndrome have been linked to mutations in PYCR1 or ALDH18A1. A 2017 report described two siblings with clinically severe de Barsy syndrome in whom two novel mutations in ALDH18A1 (p.Glu100* and p.Arg724His) were found by clinical exome sequencing. The p.Glu100* mutation is predicted to cause absence of the protein. The patients suffered from severe gastro-oesophageal reflux disease with vomiting and feeding problems despite multistage therapy including Nissen fundoplication, and from epilepsy requiring complex multidrug therapy. L-Arginine (200 mg/kg) and citrulline (100 mg/kg) were supplemented in the second sibling. Because the disease leads to premature apoptosis, antioxidants (coenzyme Q, vitamin A and E) as well as carnitine were supplemented but without spectacular clinical results. A 2023 case from Colombia noted that there is no specific treatment and management is done according to associated alterations.
The 2017 report found that the level of ammonia in serum was in the normal range in the second sibling, while the amino acid profile showed decreased concentrations of arginine, citrulline, homocysteine, phenylalanine and ornithine. The 2023 Colombian report stated that diagnosis is usually difficult due to the few cases reported worldwide and requires molecular or histopathological studies. What remains missing is any controlled trial of supplementation, a clear understanding of which patients might benefit from arginine or citrulline, and sufficient patient numbers to stratify by genotype or severity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Pediatric Orthopaedics · 1994 · 25 citations
Orthopaedic Manifestations in de Barsy Syndrome
Abstractde Barsy syndrome is a rare, genetically transmitted condition characterized by severe cutis laxa, joint hypermobility, growth retardation, mental retardation, and characteristic facies. Affected individuals have many orthopaedic manifestations, including developmental dysplasia of the hip, scoliosis, multiple joint dislocations and subluxations, and congenital vertical talus. The management of the orthopaedic manifestations of this syndrome is presented in two typical cases.
The Turkish Journal of Pediatrics · 2001 · 5 citations · open access
The de Barsy syndrome
AbstractWe report a child with de Barsy syndrome, which is a very rare, genetically transmitted clinical entity associated with mental and growth retardation, severe cutis laxa, joint laxity and various ocular and skeletal system findings. The patient was operated to treat her orthopedic disabilities. Typical findings of this case with eight-year follow-up beginning from birth are described and compared with previously reported cases. The main aim of this paper was to describe the diagnostic and therapeutic difficulties of this rarely encountered syndrome.
Journal of Clinical & Medical Genomics · 2017 · 2 citations · open access
Severe Phenotype of De Barsy Syndrome in Two Siblings with Novel Mutations in the ALDH18A1 Gene
AbstractDe Barsy syndrome is a rare autosomal recessive genetic disorder characterized by growth retardation, intellectual disability, a prematurely-aged appearance (progeroid features) and loose skin (cutis laxa) as well as eye abnormalities and others. Some cases of de Barsy syndrome have been linked with mutations PYCR1 or ALDH18A1. We describe a family with two siblings with clinically severe de Barsy syndrome in whom two novel mutations in ALDH18A1 (p.Glu100* and p.Arg724His) were found by clinical exome sequencing using TruSight One panel. The p.Glu100* is a novel mutation predicted to cause absence of the protein. The p.Arg724His has been found with low frequency (0.000016) but not in association with human disease; it has been scored as pathogenic by CADD, MetaSVM, Polyphen2, MutationAssessor, SIFT and MutationTaster. The level of ammonia in serum was determined in second sibling and was in normal range. Amino acid profile in serum revealed decreased concentration of arginine, cytruline, homocysteine, PHE and ornithine. The patients suffer from severe symptoms of GERD such as vomiting, feeding problems instead of multistage therapy including Nissen fundoplication procedure as well as from epilepsy requires complex multidrug therapy. L-Arginine (200 mg/kg) and citrulline (100 mg/kg) were supplemented in the second sibling. The disease leads to premature apoptosis, so antioxidants (coenzyme Q, vitamin A and E) as well as carnitine were supplemented but without spectacular clinical results.
We provide clinical description of severe phenotype of de Barsy syndrome. Our molecular report broadens the spectrum of ALDH18A1 mutations causing de Barsy syndrome.
Journal of Cutaneous Pathology · 2009 · 0 citations
Suatu Penelitian Mengenai Gambaran Academic Adjusment pada Mahasiswa Angkatan 2007 di Fakultas Psikologi Universitas "X" BAndung
AbstractClinical, phenotypic, and structural data were consistent with the diagnosis of De Barsy syndrome. This is the first case described in Italy. Clinical and structural data confirm that the elastic component is mostly affected in this disorder. Moreover, ultrastructural and immunochemical findings suggest that both elastic fiber degradative and very likely synthetic processes are involved.
International Journal of Science and Research (IJSR) · 2023 · 0 citations · open access
De Barsy Syndrome (DBS): First Case Reported in Colombia
AbstractDe Barsy syndrome (DBS) is an infrequent autosomal recessive disease, where a relationship has been identified in ALDH18A1 and PYCR1 mutations, mainly producing cutis laxa in the affected patient. Other clinical characteristics are similar to patients with Progeria Syndrome. Diagnosis is usually difficult due to the few cases reported worldwide. In order to identify patients with DBS molecular and/or histopathological studies are necessary.There is no specific treatment in these patients, and management is done according to the associated alterations.Probably, the first case described in Colombia with DBS is described.
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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