DeCure for Polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly — 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 modulePolycystic lipomembranous osteodysplasia with sclerosing leukoencephaly 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 polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly 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
triggering receptor expressed on myeloid cells 2 (TREM2) — TREM2 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 6B8O · 2.2 Å · ligand 1,2-DICAPROYL-SN-PHOSPHATIDYL-L-SERINE (PSF). Experimental structure, not a prediction.
What the evidence adds up to
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, also called Nasu-Hakola disease, is a rare and fatal autosomal recessive disorder. About 160 cases had been reported by 1998, mostly in Finland and Japan. The clinical course is characterised by bilateral lytic bone lesions in the arms and legs, often causing painful pathologic fractures, followed by rapid progression of presenile dementia and death in the fifth decade of life. A 2006 report of five patients, three of them siblings, states that a biopsy is not needed for diagnosis because the combination of radiographic and neurologic features is unique. The radiographic changes can be confused with cystic angiomatosis, focal metastasizing hemangioendothelioma, or Langerhans' cell histiocytosis.
The etiology and pathogenesis were unknown in both 1983 and 1998. In 1983, two patients, a 22-year-old woman and a 30-year-old man, were described with no apparent cause; histologically, the bone lesions consisted of convoluted membranes interlaced with lipoid structures. By 1998, the locus for the disease in the Finnish population had been assigned to chromosome 19q13.1, and fine-scale mapping restricted the critical region to 153 kilobases. Strong linkage disequilibrium was detected, with a multipoint P value below 10⁻⁴⁷, and all Finnish disease chromosomes shared a core haplotype between markers D19S1175 and D19S608. A promising positional candidate, an amyloid precursor-like protein, was sequenced but no mutations were found.
No treatment, drug, or intervention of any kind is mentioned in any of these abstracts. The natural history is uniformly fatal, with dementia progressing rapidly and death occurring in the fifth decade. What is still missing is any understanding of the molecular mechanism, any animal model, any therapeutic target, and any clinical trial. The gene itself had not yet been cloned as of 2006, and no patient stratification beyond the Finnish founder haplotype had been achieved. Money for basic gene discovery and functional studies, rather than for clinical trials, was the gap.
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 Orthopaedics and Related Research · 2006 · 28 citations
Nasu-Hakola Disease (PLOSL)
AbstractThe combination of bilateral lytic lesions in the bones of the lower and upper extremities and presenile dementia is characteristic of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease. The clinical course of this rare and fatal disorder is characterized by pathologic fractures of these often painful lesions, rapid progression of dementia, and death in the fifth decade of life. The radiographic changes may be confused with cystic angiomatosis, focal metastasizing hemangioendothelioma, or Langerhans' cell histiocytosis. We report five patients to illustrate the clinical presentation, radiographic images, psychiatric abnormalities, and new genetic findings. Three of the patients were siblings. A biopsy is not needed to confirm the diagnosis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy because of the unique combination of radiographic and neurologic features.
Fine-Scale Mapping of a Novel Dementia Gene, PLOSL, by Linkage Disequilibrium
AbstractPolycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; MIM 221770) is a rare hereditary cause of presenile dementia with autosomal recessive inheritance. Its unique feature is the cystic bone lesions that accompany the dementia. About 160 cases have been reported to date, mostly in Finland and Japan. The etiology and pathogenesis of PLOSL are unknown. We recently assigned the locus for PLOSL in the Finnish population to chromosome 19q13.1 (P. Pekkarinen et al., 1998, Am. J. Hum. Genet. 62, 362-272). In the present study, we restrict the critical region for PLOSL to 153 kb by linkage-disequilibrium mapping. First, three new microsatellite markers were revealed in the PLOSL critical region. These and three other markers spanning the critical region were analyzed in Finnish PLOSL families. Strong linkage disequilibrium (multipoint P value < 10(-47)) was detected between the markers and PLOSL, and for two markers, D19S1176 and D19S610, all the PLOSL chromosomes shared identical 171- and 218-bp alleles, respectively. Haplotype analysis revealed five different haplotypes in the Finnish PLOSL chromosomes. But all of them shared the region between markers D19S1175 and D19S608 that could be traced to one ancestor haplotype by single recombination events, thus defining the critical region as 153 kb. Multipoint association analysis also assigned the most likely location of the PLOSL locus within this interval to the immediate vicinity of marker D19S610. A promising positional candidate for PLOSL, an amyloid precursor-like protein, was studied by sequencing, but no mutations were detected. These results lay the basis for the cloning of this novel dementia gene and for diagnostics in the Finnish population using haplotype analysis.
AbstractMembranous lipodystrophy, a hereditary disease, is characterized by symmetric multiple cystic bone lesions and progressive neuropsychiatric symptoms. In two patients, a 22-year-old woman and a 30-year-old man, as in others reported in the literature, neither the etiology nor the pathogenesis was apparent. Histologically, the lesions consisted of convoluted membranes interlaced with lipoid structures.
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.
