DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Lenz-Majewski hyperostotic dwarfism — 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 moduleLenz-Majewski hyperostotic dwarfism 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 lenz-majewski hyperostotic dwarfism 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
phosphatidylserine synthase 1 (PTDSS1) — PTDSS1 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 psfdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9KQJ · 2.95 Å · ligand 1,2-DICAPROYL-SN-PHOSPHATIDYL-L-SERINE (PSF). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2022 · 7 citations · open access
De novo loss‐of‐function variant in <scp><i>PTDSS1</i></scp> is associated with developmental delay
AbstractAbstract Heterozygous de novo missense pathogenic variants in PTDSS1 that result in gain‐of‐function of phosphatidylserine synthase 1 are associated with Lenz–Majewski hyperostotic dwarfism (LMHD). We identified the novel heterozygous de novo variant p.(Leu137Phe) in PTDSS1 in a child with mild‐to‐moderate developmental delay. Skeletal survey revealed no evidence of LMHD in this patient. Functional assessment of the p.Leu137Phe variant was performed by overexpressing the mutant protein into HEK293 cells. Following C 14 ‐serine labeling and TLC analysis of lipids, we observed that the p.(Leu137Phe) variant displayed no catalytic activity compared to the wild‐type enzyme. We conclude that p.(Leu137Phe) variant has decreased enzymatic activity and that is likely to be the etiology of the patient's symptoms given the gene's constraint in the population. This is the first report of the clinical phenotype seen in an individual with a heterozygous loss‐of‐function variant in PTDSS1 . This phenotype is distinct from LMHD, which results from gain‐of‐function pathogenic variants in the same gene. Evaluation of the neurodevelopmental phenotype of additional individuals with loss‐of‐function variants in PTDSS1 is indicated to determine the spectrum of associated phenotypes.
European Journal of Medical Genetics · 2024 · 4 citations · open access
Lenz-Majewski syndrome and recurrent otitis media: Are they related or not?
AbstractLenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even rarer features such as hydrocephalus, facial paralysis, and cleft palate. We, hereby, report the case of the first patient with Lenz-Majewski syndrome (LMS) with molecular confirmation from Turkey. Although our patient had characteristic features described in the literature, she also had immunodeficiency, which has not been reported before. Although there is no established phenotype-genotype correlation, molecular mechanisms can be explained with the reporting of more patients.
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.
