DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for acromesomelic dysplasia 2B — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcromesomelic dysplasia 2B maps to a 3-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 acromesomelic dysplasia 2b 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
bone morphogenetic protein receptor type 1B (BMPR1B) — BMPR1B 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 4-piperazin-1-ylphenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3MDY · 2.05 Å · ligand 4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline (LDN). Experimental structure, not a prediction.
What the evidence adds up to
Acromesomelic dysplasia 2B is one of several acromesomelic dysplasias, a group of skeletal disorders with autosomal recessive inheritance that cause extremely short stature and limb abnormalities. The 1980 paper describes the radiographic features that allow diagnosis after six months of age. No treatment is mentioned in any of the abstracts.
Mutations in four genes have been linked to different subtypes. A 2018 study of a consanguineous Pakistani family with the Hunter–Thompson type identified a novel homozygous missense variant in BMPR1B (c.1190T>G, p.Met397Arg) with a LOD score of 3.9. A 2019 report on the Maroteaux type in Vietnamese patients found a novel homozygous variant in NPR2 (c.152T>C, p.Leu51Pro) in the proband, with heterozygous carrier parents and two other family members. A 2016 paper identified heterozygous mutations in LTBP3 in dominant acromicric dysplasia and two de novo heterozygous LTBP3 mutations in two unrelated children with geleophysic dysplasia who died in early childhood from respiratory failure; the authors concluded LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.
No drug, no therapy, and no clinical trial is described in any of these abstracts. What remains missing is any treatment strategy, any animal model testing of a repurposed compound, any funding for such work, and any patient stratification beyond the known genetic subtypes.
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.
AbstractThe radiographic features of acromesomelic dysplasia are presented, along with a summary of pertinent clinical features. They are thought to allow a diagnosis in affected individuals over six months of age. Since the condition has an autosomal recessive mode of genetic transmission and results in extremely short stature, the establishment of the diagnosis has practical importance.
A novel homozygous variant in <i>BMPR1B</i> underlies acromesomelic dysplasia Hunter–Thompson type
AbstractAcromesomelic dysplasia is genetically heterogeneous group of skeletal disorders characterized by short stature and acromelia and mesomelia of limbs. Acromesomelic dysplasia segregates in an autosomal recessive pattern and is caused by biallelic sequence variants in three genes (NPR2, GDF5, and BMPR1B). A consanguineous family of Pakistani origin segregating a subtype of acromesomelic dysplasia called Hunter-Thompson was clinically and genetically evaluated. Genotyping of microsatellite markers and linkage analysis revealed a 7.78 Mb homozygous region on chromosome 4q22.3, which harbors BMPR1B. Sequence analysis of the gene revealed a novel homozygous missense variant (c.1190T > G, p.Met397Arg) that segregates with the disease phenotype within the family and produced a Logarithm of odds (LOD) score of 3.9 with the disease phenotype. This study reports on the first familial case of acromesomelic dysplasia Hunter-Thompson type. It is also the first report of BMPR1B underlying the etiology of acromesomelic dysplasia Hunter-Thompson type.
American Journal of Medical Genetics Part A · 2019 · 6 citations
Acromesomelic dysplasia Maroteaux‐type in patients from Vietnam
AbstractAcromesomelic dysplasias are rare skeletal disorders leading to severe short stature and abnormal skeletal morphology. Acromesomelic dysplasia Maroteaux-type is caused by homozygous or compound heterozygous pathogenic variants in NPR2 that encodes for natriuretic peptide receptor B. Here, we reported the first AMDM case in South East Asia and identified a novel pathogenic variant in NPR2 (c. 152T>C, p. (Leu51Pro)). Further analyses reveal the parents and two other family members were heterozygous for the variant. The clinical report highlights the importance of molecular genetic testing in diagnosing rare hereditable disease affecting skeletal abnormalities.
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.
