DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Boomerang dysplasia — 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 moduleBoomerang dysplasia 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 boomerang 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
filamin B (FLNB) — FLNB 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 4B7L · 2.05 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Boomerang dysplasia is a perinatal lethal osteochondrodysplasia defined by absent or underossified limb bones and vertebrae. In 2005, mutations in the FLNB gene, which encodes the actin-binding cytoskeletal protein filamin B, were identified in two unrelated individuals with the condition. The substitutions L171R and S235P lie within the calponin homology 2 region of the actin-binding domain and occur at evolutionarily well-conserved sites. These findings expanded the phenotypic spectrum of FLNB mutations, which also cause atelosteogenesis I, atelosteogenesis III, and dominantly inherited Larsen syndrome.
A 2003 case report described prenatal detection of boomerang dysplasia by ultrasound at 16 weeks of gestation, noting micromelia with diminished ossification and a characteristic bowed, boomerang-like appearance of the long tubular bones. No treatment or intervention was reported in that case.
A 2020 computational study retrieved 285 FLNB missense variants from public databases, of which five were in the CH1 domain and 39 in the CH2 domain. Molecular dynamics simulation was performed on three CH2 domain variants predicted to be most pathogenic: W148R, F161C, and L171R. The simulations showed these three variants produced proteins that were highly compact compared to the native protein, suggesting structural and functional disruption. The study explicitly states that the genotype-phenotype correlation for FLNB-related disorders remains enigmatic, and that the computational approach may pave the way for optimising drug therapy by integrating precision medicine — but no drug, therapy, or clinical trial is described or tested.
What is still missing: any clinical trial or preclinical study testing a drug for boomerang dysplasia; any animal model of the condition treated with a compound; any patient-derived cell work showing drug response; and any funding or trial design aimed at repurposing an existing drug for this lethal disorder. The disorder is defined by specific FLNB mutations, but no pharmacological intervention has been reported in the literature.
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 · 2005 · 82 citations · open access
Mutations in <i>FLNB</i> cause boomerang dysplasia
AbstractBoomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia, characterised by absence or underossification of the limb bones and vertebrae. The BD phenotype is similar to a group of disorders including atelosteogenesis I, atelosteogenesis III, and dominantly inherited Larsen syndrome that we have recently shown to be associated with mutations in FLNB, the gene encoding the actin binding cytoskeletal protein, filamin B. We report the identification of mutations in FLNB in two unrelated individuals with boomerang dysplasia. The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain of filamin B and occur at sites that are evolutionarily well conserved. These findings expand the phenotypic spectrum resulting from mutations in FLNB and underline the central role this protein plays during skeletogenesis in humans.
American Journal of Medical Genetics Part A · 2003 · 16 citations
Prenatal diagnosis of boomerang dysplasia
AbstractBoomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang-like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound.
Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome, Boomerang Dysplasia, and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach
AbstractFilamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.
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.
