DeCure for Leukoencephalopathy with vanishing white matter 5
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for leukoencephalopathy with vanishing white matter 5 — 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 moduleLeukoencephalopathy with vanishing white matter 5 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 leukoencephalopathy with vanishing white matter 5 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
eukaryotic translation initiation factor 2B subunit epsilon (EIF2B5) — EIF2B5 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 9Y4B · 2.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Leukoencephalopathy with vanishing white matter is an inherited disorder with a chronic progressive course and additional episodes of rapid neurological deterioration. These episodes are typically provoked by febrile infections or minor head trauma. Two patients experienced an episode of rapid neurological deterioration after a fright, suggesting that emotional stress may also act as a provoking factor.
A 2025 case report describes a 39-year-old man with adult-onset vanishing white matter leukoencephalopathy who presented with postural instability, imbalanced gait, progressive lower extremity deterioration, ocular abnormalities, and sphincteric issues. Neurological examination revealed reduced cognitive function, spastic quadriparesis, hyperreflexia, bradykinesia, and shuffling gait. MRI showed periventricular white matter hyperintensities. Genetic testing identified a homozygous pathogenic missense variant in EIF2B3 and a deletion in PRKN/PARK2. The patient’s motor symptoms were temporarily alleviated following administration of Levodopa/Carbidopa, but the long-term consequences are uncertain due to the illness’s ongoing progression and the absence of a cure. A 2013 case of fatal vanishing white matter disease with unexplained hypertension was linked to a homozygous EIF2B5 mutation; the report notes the disease leads to slowly progressive neurologic deterioration with episodes of rapid clinical worsening and eventually death.
A separate 2018 study of 173 long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only found leukoencephalopathy in 52 survivors (30.0%), persisting in 41 of 52 (78.8%) who developed it during therapy. DTI parameters were associated with leukoencephalopathy in multiple brain regions, and mean diffusivity was associated with neurocognitive impairment. This study concerns chemotherapy-related leukoencephalopathy, not the inherited vanishing white matter disease, and does not test any drug for the inherited condition.
What is still missing: a cure for vanishing white matter disease remains unknown. The 2025 case notes that early discovery is crucial to manage symptoms but that long-term consequences are uncertain. No clinical trial data exist for any drug specifically targeting the inherited disorder in a controlled setting. More research is needed, particularly in regions where studies on neurological disorders are limited, and the field lacks patient stratification strategies and adequately funded trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2005 · 59 citations
Fright is a provoking factor in vanishing white matter disease
AbstractLeukoencephalopathy with vanishing white matter is an inherited disorder with a chronic progressive disease course and additional episodes of rapid neurological deterioration. These episodes typically are provoked by febrile infections or minor head trauma. We report on two patients who experienced an episode of rapid neurological deterioration after a fright.
American Journal of Neuroradiology · 2018 · 29 citations · open access
The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only
Abstract<h3>BACKGROUND AND PURPOSE:</h3> Survivors of acute lymphoblastic leukemia are at risk for neurocognitive deficits and leukoencephalopathy. We performed a longitudinal assessment of leukoencephalopathy and its associations with long-term brain microstructural white matter integrity and neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a modern chemotherapy-only protocol. <h3>MATERIALS AND METHODS:</h3> One hundred seventy-three survivors of acute lymphoblastic leukemia (49% female), treated on a chemotherapy-only protocol, underwent brain MR imaging during active therapy and repeat imaging and neurocognitive testing at follow-up (median, 13.5 years of age; interquartile range, 10.7–17.6 years; median time since diagnosis, 7.5 years; interquartile range, 6.3–9.1 years). Persistence of leukoencephalopathy was examined in relation to demographic and treatment data and to brain DTI in major fiber tracts and neurocognitive testing at follow-up. <h3>RESULTS:</h3> Leukoencephalopathy was found in 52 of 173 long-term survivors (30.0%) and persisted in 41 of 52 (78.8%) who developed it during therapy. DTI parameters were associated with leukoencephalopathy in multiple brain regions, including the corona radiata (fractional anisotropy, <i>P</i> = .001; mean diffusivity, <i>P</i> < .001), superior longitudinal fasciculi (fractional anisotropy, <i>P</i> = .02; mean diffusivity, <i>P</i> < .001), and superior fronto-occipital fasciculi (fractional anisotropy, <i>P</i> = .006; mean diffusivity, <i>P</i> < .001). Mean diffusivity was associated with neurocognitive impairment including in the genu of the corpus callosum (<i>P</i> = .04), corona radiata (<i>P</i> = .02), and superior fronto-occipital fasciculi (<i>P</i> = .02). <h3>CONCLUSIONS:</h3> Leukoencephalopathy during active therapy and neurocognitive impairment at long-term follow-up are associated with microstructural white matter integrity. DTI may be more sensitive than standard MR imaging for detection of clinically consequential white matter abnormalities in childhood acute lymphoblastic leukemia survivors treated with chemotherapy and in children undergoing treatment.
A rare case of adult-onset vanishing white matter leukoencephalopathy with movement disorder, expressing homozygous EIF2B3 and PRKN pathogenic variants
AbstractBACKGROUND: Vanishing white matter disease (VWMD) is a rare autosomal recessive leukoencephalopathy. It is typified by a gradual loss of white matter in the brain and spinal cord, which results in impairments in vision and hearing, cerebellar ataxia, muscular weakness, stiffness, seizures, and dysarthria cogitative decline. Many reports involve minors. Very few instances worldwide have been reported, with adult onset of vanishing white matter considered to account for 15% of cases. Clinical evaluation, MRI results, and confirmatory genetic testing are used to diagnose VWMD. CASE PRESENTATION: A 39-year-old male from Hebron, Palestine, presented with a 7-month history of postural instability, imbalanced gait, and progressive deterioration of his lower extremities. Additionally, the patient suffered from ocular abnormalities and sphincteric issues. The patient's sibling showed comparable symptoms but was never diagnosed, as he passed away because of colon cancer. Reduced cognitive function, spastic quadriparesis, hyperreflexia, bradykinesia, and shuffling gait were found during a neurological examination. Normal results were obtained from routine laboratory tests, including cerebrospinal fluid (CSF), blood, and urine. Periventricular white matter hyperintensities, which are indicative of vanishing white matter leukoencephalopathy (VWML), were identified during an MRI. The diagnosis of adult-onset VWML with movement disability was substantiated by genetic testing, which named a homozygous pathogenic missense variant, EIF2B3, and a deletion in PRKN/PARK2. The patient's motor symptoms were temporarily alleviated following the administration of Levodopa/Carbidopa. Nevertheless, the long-term consequences are uncertain due to the illness's ongoing progression and the absence of a cure currently. CONCLUSION: This instance of vanishing white matter leukoencephalopathy (VWML) is particularly remarkable in adults because of its rarity and complexity. The diagnosis is further complicated by the coexistence of Parkinsonism and VWML. Although a cure is not currently known. Early discovery is crucial to effectively manage symptoms. This example underscores the importance of more VWML research, particularly in Palestine, where studies on neurological disorders are limited. These findings underscore the importance of enhancing the region's diagnostic and therapeutic capabilities.
International journal of Nutrition Pharmacology Neurological Diseases · 2013 · 1 citations
Fatal vanishing white matter disease with unexplained hypertension due to E1F2B5 homozygous mutation
AbstractVanishing white matter is an autosomal recessive leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B. It is a disease of infants, children and adults who experience a slowly progressive neurologic deterioration with episodes of rapid clinical worsening and eventually leading to death. We report a classical case to highlight its clinical significance.
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.
