DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lateral meningocele syndrome — 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 moduleLateral meningocele syndrome 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 lateral meningocele syndrome 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
notch receptor 3 (NOTCH3) — NOTCH3 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 5CZX · 2.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Lateral meningocele syndrome is an exceedingly rare connective tissue disease. As of 2019, a literature review identified 11 articles describing 16 cases, 9 male and 7 female, from 14 different families. The syndrome is characterised by multiple lateral thoracolumbar spinal meningoceles and distinctive craniofacial features, alongside skeletal abnormalities. Autosomal dominant inheritance is supported by a reported affected mother and daughter. The etiopathogenesis has been linked to truncating mutations within exon 33 of NOTCH3; half of the 16 reviewed cases underwent genetic screening, and all of those were found to have such a mutation.
The phenotype has been expanded beyond the core features. One simplex case presented with a bicuspid aortic valve, supporting a connective tissue basis. Another 3-month-old patient with metopic craniosynostosis was found to have two NOTCH3 variants, leading to a diagnosis of lateral meningocele (Lehman) syndrome. This patient also had an increased possibility of stroke associated with CADASIL, which altered surgical management: she underwent only anterior calvarial vault remodelling without fronto-orbital advancement. A 61-year-old female with LMS developed multiple chemical sensitivity syndrome, though the authors frame this as a possible unlucky coincidence.
Neurosurgical management of the multiple spinal meningoceles is complex and poorly defined. Coexisting structural neurologic pathologies reported in these patients include Chiari I malformation, syringomyelia, hydrocephalus, tethered cord, and pathologic changes in spine morphology. These conditions alter cerebrospinal fluid flow dynamics and complicate operative intervention. A separate case series of congenital basal meningoceles (not specifically LMS) reported that one patient died of sepsis after traumatic rupture of an undiagnosed meningocele during nasal suction; two others underwent surgical repair without complications.
What is still missing is a standardised neurosurgical management protocol for LMS, given the small number of reported cases and the confounding effect of coexisting neuropathology. Larger patient cohorts, prospective data collection, and clearer stratification of patients by specific NOTCH3 mutation type and associated structural anomalies are needed before any reliable guidance on operative timing or technique can be established.
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 · 2005 · 36 citations
Lateral meningocele syndrome: Vertical transmission and expansion of the phenotype
AbstractLateral meningoceles were first described by Lehman et al. [(1977); J Pediatr 90: 49-54] in a patient with other skeletal findings and distinctive craniofacial features. Subsequently, six more patients with the so-called lateral meningocele syndrome (LMS) have been reported. We describe the findings in three new cases and expand the phenotype. The existence of an affected mother and daughter supports the hypothesis that LMS is a dominant disorder affecting primarily the connective tissue.
American Journal of Medical Genetics Part A · 2013 · 16 citations
Lateral meningocele syndrome: Additional report and further evidence supporting a connective tissue basis
AbstractLateral meningocele syndrome is a rare disorder of unknown etiology, first described in 1977 and subsequently reported in nine other patients. These patients present distinctive craniofacial features and skeletal abnormalities in addition to multiple lateral meningoceles, suggesting a connective tissue disorder. Autosomal dominant inheritance is clearly suggested in one family and could explain familiar aggregation in another. We describe a simplex case of lateral meningocele syndrome with bicuspid aortic valve, supporting the hypothesis of a connective tissue basis for this disorder and further expanding the phenotype.
Journal of Medical Case Reports · 2017 · 8 citations · open access
Congenital basal meningoceles with different outcomes: a case series
AbstractBACKGROUND: Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis. CASE PRESENTATION: We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring. CONCLUSIONS: These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications.
Pediatric Neurosurgery · 2019 · 8 citations · open access
Neurosurgical Management of Lateral Meningocele Syndrome: A Clinical Update for the Pediatric Neurosurgeon
AbstractBACKGROUND: Lateral meningocele syndrome (LMS) is an exceedingly rare connective tissue disease with phenotypic anomalies similar to those seen in Marfan syndrome, Ehler-Danlos syndrome, and Loeys-Dietz syndrome. However, this syndrome is invariably associated with the presence of multiple lateral thoracolumbar spinal meningoceles: a distinct point of phenotypic divergence from other connective tissue disorders. The etiopathogenesis of this syndrome has recently been linked to truncating mutations within exon 33 of NOTCH3. Despite numerous reports, neurosurgical management of multiple spinal meningoceles remains poorly defined in the literature. We conducted a literature review to provide insight into the nosology, clinical significance, and neurosurgical management strategies of this distinct connective tissue disorder. SUMMARY: Our literature search revealed 11 articles (16 cases) of LMS, which included 9 males and 7 females, belonging to 14 different families. Half of these cases underwent genetic screening: all of which were discovered to exhibit a truncating mutation within exon 33 of NOTCH3. All patients exhibited multiple lateral thoracolumbar spinal meningoceles with craniofacial dysmorphisms. Other clinical characteristics included pathologic changes in spine morphology, Chiari I malformation, syringomyelia, hydrocephalus, and tethered cord. Operative management of multiple spinal meningoceles in LMS is complicated by the presence of such coexisting structural neurologic pathologies, which may alter cerebrospinal fluid flow dynamics and, ultimately, impact operative intervention. Key Messages: LMS is an exceedingly rare connective tissue disorder with severe spinal dural involvement. Neurosurgical management of multiple spinal meningoceles is complex, which is further complicated by the presence of coexisting neuropathology, such as pathologic transformation of spine morphology and Chiari I malformation. Patients with a connective tissue disorder phenotype found to have multiple spinal meningoceles on imaging studies may benefit from evaluation by a medical geneticist and a pediatric neurosurgeon.
Journal of Craniofacial Surgery · 2021 · 1 citations
Craniosynostosis of the Metopic Suture in a Patient With CADASIL/Lehman Syndrome
AbstractABSTRACT: A 3-month-old patient presented for evaluation by plastic surgery with marked trigonocephaly and was subsequently diagnosed with metopic craniosynostosis. During presurgical evaluation, the patient was found to have two variants of the NOTCH3 gene, resulting in the diagnosis of lateral meningocele (Lehman) syndrome. Due to the increased possibility of stroke associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the patient underwent only anterior calvarial vault remodeling without fronto-orbital advancement for correction of her craniosynostosis. This unique constellation of symptoms, and its impact on operative management, has not been previously described in the literature.
DOAJ (DOAJ: Directory of Open Access Journals) · 2018 · 1 citations · open access
De novo appearance of multiple chemical sensitivity syndrome in a patient affected with lateral meningocele syndrome: unlucky coincidence?
AbstractAlthough the coexistence of rare pathologies in the same patient is considered an exceptional event, the possibility to contend with a condition such like this may occur in clinical practice. In these cases, a multidisciplinary approach is required in order to find the most appropriate therapeutic strategy. Here we describe the clinical case of a 61 years old female affected with a rare genetic pathology known as lateral meningocele syndrome (LMS) who developed a pathological condition that could be framed in the context of a multiple chemical sensitivity syndrome (MCSS) characterized by intolerance to several drugs, foods as well as environmental and chemical agents.
AbstractLateral meningocele syndrome, also known as Lehman syndrome, is an exceptionally uncommon genetic disorder, which is characterized by specific facial features and multisystem involvement, including skeletal, cardiac, and urogenital anomalies, akin to other connective tissue disorders, but it is set apart by the unique occurrence of multiple lateral meningoceles. Knowledge of the distinctive imaging features can strongly suggest the diagnosis in patients with complex clinical presentations to assist in the guidance of appropriate and timely clinical management.
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.
