DeCure for Mandibuloacral dysplasia with type B lipodystrophy
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for mandibuloacral dysplasia with type B lipodystrophy — 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 moduleMandibuloacral dysplasia with type B lipodystrophy 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 mandibuloacral dysplasia with type b lipodystrophy 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
zinc metallopeptidase STE24 (ZMPSTE24) — ZMPSTE24 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 pc1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AW6 · 3.4 Å · ligand 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PC1). Experimental structure, not a prediction.
What the evidence adds up to
Mandibuloacral dysplasia with type B lipodystrophy is a very rare autosomal recessive disease. A 1984 report of two brothers confirmed Welsh’s earlier hypothesis of autosomal recessive inheritance, and noted the syndrome is probably often misdiagnosed. The disease is caused by mutations in ZMPSTE24, a gene encoding a zinc metalloproteinase involved in lamin processing. By 2016, nine distinct pathogenic variants had been identified in 11 patients from nine unrelated families.
A 2016 report described a 12-year-old boy with a novel homozygous c.1196A>G; p.(Tyr399Cys) mutation in ZMPSTE24. He had typical dermatological and skeletal features, sparse hair, short stature, mild microcephaly, facial dysmorphism, and a striking failure of ossification of the interparietal region of the occipital bone. Newly recognised signs were gaze palsy and ptosis. Delayed closure of cranial sutures and Wormian bones had been described in three patients, but an ossification failure strictly limited to the occipital bone appeared unique to this case. The authors suggested this failure of ossification in the squama is a useful radiological diagnostic feature. A 2019 report from Chile described the first case in that country, a patient with two compound heterozygous variants in ZMPSTE24: c.1085dup p.(Leu362Phefs*19) and c.794A>G p.(Asn265Ser).
No treatment or drug intervention is mentioned in any of these abstracts. The entire literature consists of case reports and genetic descriptions. What is missing is any clinical trial, any drug being tested, any systematic natural history study with standardised outcome measures, and any patient stratification beyond mutation type. Funding for therapy development and a trial design that can measure meaningful endpoints in a disease this rare remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 1984 · 21 citations
Mandibuloacral dysplasia: a rare progeroid syndrome Two brothers confirm autosomal recessive inheritance
AbstractMandibuloacral Dysplasia would appear to be a very rare syndrome, probably because it is usually mistakenly diagnosed. This article describes the case histories of two brothers, confirming Welsh's (1975) earlier hypothesis concerning autosomal recessive inheritance and makes certain observations which should be helpful in diagnosing this rare hereditary syndrome.
American Journal of Medical Genetics Part A · 2019 · 6 citations
Mandibuloacral dysplasia with type B lipodystrophy in a patient from Chile
AbstractWe report the first case of mandibuloacral dysplasia with type B lipodystrophy (MADB) in Chile, South America. MADB is a very rare illness, characterized by short stature, mandibular hypoplasia, acro-osteolysis in hands, feet and clavicles, lipodystrophy, changes in skin pigments and skin calcinosis at knees and hands. Diagnosis was confirmed by molecular study that showed two compound heterozygous variants in ZMPSTE24 gene, c.1085dup p.(Leu362Phefs*19) and c.794A>G p.(Asn265Ser). This article could help in establishing the correlation between genotype and phenotype of this disorder, comparing with other cases previously 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.
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.
