DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for acrodysostosis — 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 moduleAcrodysostosis 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 acrodysostosis 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
protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) — PRKAR1A 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 pcgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KJZ · 1.347 Å · ligand CYCLIC GUANOSINE MONOPHOSPHATE (PCG). Experimental structure, not a prediction.
What the evidence adds up to
Three unrelated patients with acrodysostosis and resistance to multiple hormones were found to carry a germ-line mutation in PRKAR1A, the gene encoding the cAMP-dependent regulatory subunit of protein kinase A. The mutated subunit impairs the protein kinase A response to stimulation by cAMP, which explains the hormone resistance and the skeletal similarities to pseudohypoparathyroidism type 1a. No GNAS defects were present in these patients.
An 8-year-old boy with midface hypoplasia, hypertelorism, prominent nasal bridge, small upturned nostrils, broad thumb and great toes, and brachydactyly of remaining fingers and toes was found to carry a heterozygous c.1813T>C (p.Tyr605His) missense mutation in PDE4D. This mutation was not found in either parent and was previously unreported. The child was diagnosed with acrodysostosis type 2.
A 19-year-old woman with acrodysostosis presented with progressively worsening lower extremity paraparesis, sensory loss, and urinary retention, and became wheelchair-bound. MRI showed cord signal change at T2/T3 with diffuse cord edema between T6 and T8. Six months after laminectomy at T2/T3 and T6/T7, her symptoms improved but she still required a wheelchair. The authors recommend regular monitoring for cord compression to allow early surgical decompression.
No drug treatment for acrodysostosis is described in these abstracts. What is missing is any clinical trial of a pharmacological intervention, any attempt to target the PRKAR1A or PDE4D pathways therapeutically, and any systematic study of whether patient stratification by mutation type could alter management.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2011 · 181 citations · open access
Recurrent <i>PRKAR1A</i> Mutation in Acrodysostosis with Hormone Resistance
AbstractThe skeletal dysplasia characteristic of acrodysostosis resembles the Albright's hereditary osteodystrophy seen in patients with pseudohypoparathyroidism type 1a, but defects in the α-stimulatory subunit of the G-protein (GNAS), the cause of pseudohypoparathyroidism type 1a, are not present in patients with acrodysostosis. We report a germ-line mutation in the gene encoding PRKAR1A, the cyclic AMP (cAMP)-dependent regulatory subunit of protein kinase A, in three unrelated patients with acrodysostosis and resistance to multiple hormones. The mutated subunit impairs the protein kinase A response to stimulation by cAMP; this explains our patients' hormone resistance and the similarities of their skeletal abnormalities with those observed in patients with pseudohypoparathyroidism type 1a.
[Genetic analysis of a child with acrodysostosis type 2].
AbstractOBJECTIVE: To analyze the clinical characteristics and genetic variation in a child with acrodysostosis type 2. METHODS: The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples from him and his parents. High-throughput sequencing was carried out. The result was verified by Sanger sequencing. RESULTS: The 8-year-old boy presented with midface hypoplasia, hypertelorism, prominent nasal bridge, small and upturned nostrils, broad thumb and great toes, and brachydactyly of remaining fingers and toes. Genetic testing revealed that the child has carried a heterozygous c.1813T>C (p.Tyr605His) missense mutation of the PDE4D gene. The same mutation was not found in either parent and was unreported previously. CONCLUSION: The child was diagnosed with acrodysostosis type 2 due to the novel mutation of the PDE4D gene.
Surgical Neurology International · 2022 · 0 citations · open access
Laminectomy as treatment for abrupt neurological decline in acrodysostosis: A case report
AbstractBackground: genes. The resulting phenotypical characteristics are variable and overlap with other dysostosis conditions, making diagnosis difficult without genotyping. Vertebral malformations have been reported with ACRO resulting in slowly progressive spinal cord compression leading to radiculopathy or myelopathy. Case Description: A 19-year-old female diagnosed with ACRO presented with progressively worsening lower extremity paraparesis, sensory loss, and urinary retention; she was wheelchair-bound. A magnetic resonance imaging showed cord signal change at the T2/T3 levels with accompanying diffuse cord edema between T6-T8. Six months following a T2/T3 and T6/T7 laminectomy, the patient's symptoms improved, but she still required a wheelchair. Conclusion: Patients with ACRO should be regularly monitored for cord compression to allow for early surgical decompression to prevent long-term, devasting neurological compromise.
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.
