DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Acromicric dysplasia — 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 moduleAcromicric dysplasia 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 acromicric dysplasia 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
fibrillin 1 (FBN1) — FBN1 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 1UZK · 1.35 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In 2016, whole exome sequencing of individuals negative for mutations in known acromelic dysplasia genes identified a heterozygous missense mutation in LTBP3 (exon 14: c.2087C>G: p.Ser696Cys) in a dominant acromicric dysplasia family. Two distinct de novo heterozygous LTBP3 mutations were also found in two unrelated individuals with geleophysic dysplasia who died in early childhood from respiratory failure: a donor splice site mutation (exon 12 c.1846+5G>A) and a stop-loss mutation (exon 28: c.3912A>T: p.1304*Cysext*12). The authors concluded that LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.
A 2024 case report described a Chinese family with a heterozygous missense mutation in FBN1 (c.5179C>T, p.Arg1727Trp in exon 42). The proband and her mother were diagnosed with acromicric dysplasia, while the elder sister had geleophysic dysplasia 2 with aortic valve stenosis. The proband was treated with recombinant human growth hormone and had a body length gain of 0.72 standard deviation scores in half a year. The report notes that the efficacy of rhGH therapy in acromelic dysplasia is controversial and that more follow-up is needed on long-term efficacy.
An earlier 1987 report described a patient with geleophysic dysplasia who had progressive growth delay, mild facial anomalies, small abnormal hands, hepatosplenomegaly, and progressive cardiac valvular lesions. Electron microscopy of a liver biopsy showed changes consistent with glycoprotein storage. The authors noted that geleophysic dysplasia shares clinical and radiological manifestations with acromicric dysplasia.
No drug treatment has been shown to alter the natural history of acromicric dysplasia or geleophysic dysplasia in a controlled trial. What is missing is any prospective study of growth hormone or other agents with adequate follow-up, patient stratification by genotype, and standardised outcome measures for skeletal and cardiac disease progression.
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 Medical Genetics · 2016 · 63 citations
Mutations in <i>LTBP3</i> cause acromicric dysplasia and geleophysic dysplasia
AbstractBACKGROUND: Acromelic dysplasias are a group of disorders characterised by short stature, brachydactyly, limited joint extension and thickened skin and comprises acromicric dysplasia (AD), geleophysic dysplasia (GD), Myhre syndrome and Weill-Marchesani syndrome. Mutations in several genes have been identified for these disorders (including latent transforming growth factor β (TGF-β)-binding protein-2 (LTBP2), ADAMTS10, ADAMSTS17 and fibrillin-1 (FBN1) for Weill-Marchesani syndrome, ADAMTSL2 for recessive GD and FBN1 for AD and dominant GD), encoding proteins involved in the microfibrillar network. However, not all cases have mutations in these genes. METHODS: Individuals negative for mutations in known acromelic dysplasia genes underwent whole exome sequencing. RESULTS: A heterozygous missense mutation (exon 14: c.2087C>G: p.Ser696Cys) in latent transforming growth factor β (TGF-β)-binding protein-3 (LTBP3) was identified in a dominant AD family. Two distinct de novo heterozygous LTPB3 mutations were also identified in two unrelated GD individuals who had died in early childhood from respiratory failure-a donor splice site mutation (exon 12 c.1846+5G>A) and a stop-loss mutation (exon 28: c.3912A>T: p.1304*Cysext*12). CONCLUSIONS: The constellation of features in these AD and GD cases, including postnatal growth retardation of long bones and lung involvement, is reminiscent of the null ltbp3 mice phenotype. We conclude that LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.
American Journal of Medical Genetics · 1987 · 26 citations
Geleophysic dysplasia—acromicric dysplasia with evidence of glycoprotein storage
Abstract"Geleophysic" dysplasia is a rare autosomal recessive disorder, probably of glycoprotein metabolism, which shares some clinical and roentgenological manifestations with acromicric dysplasia. We report the clinical, radiological, and pathological data of a patient with the typical picture of progressive growth delay; mild facial anomalies; small, abnormal hands; hepatosplenomegaly; and progressive cardiac valvular lesions. Electron microscopy of a liver biopsy showed similar and additional changes to those published previously.
Datasheet1_Case Report: Two different acromelic dysplasia phenotypes in a Chinese family caused by a missense mutation in FBN1 and a literature review.docx
AbstractBackground Acromelic dysplasia caused by FBN1 mutation includes acromicric dysplasia (AD), geleophysic dysplasia 2 (GD2), and Weill-Marchesani syndrome 2 (WMS2). All three diseases share severe short stature and brachydactyly. Besides phenotypic similarity, there is a molecular genetic overlap among them, as identical FBN1 gene mutations have been identified in patients with AD, GD2, and WMS2. However, no family with different acromelic dysplasia phenotypes due to the same variant has been described in English reports. Case report The proband presented with typical facial features, severe short stature, short limbs, stubby hands and feet and radiological abnormalities. Her elder sister and mother had similar physical features. In addition, her elder sister was found to have aortic valve stenosis by echocardiography. Mutation analysis demonstrated a heterozygous missense mutation, c.5179C>T (p.Arg1727Trp) in exon 42 of the FBN1. The proband and her mother were diagnosed with AD, and her elder sister with GD2. The proband was treated with recombinant human growth hormone (rhGH) and had a body length gain of 0.72 SDS in half a year. Conclusion These findings expand the phenotypic spectrum of FBN1 gene mutations and highlight that identical FBN1 genotypes can result in different phenotypes of acromelic dysplasia in a family. The efficacy of rhGH therapy in patients with acromelic dysplasia is controversial. More follow-up is needed on the long-term efficacy of rhGH therapy.
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.
