DeCure for Leukoencephalopathy with vanishing white matter 3
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for leukoencephalopathy with vanishing white matter 3 — 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 3 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 3 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 gamma (EIF2B3) — EIF2B3 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, but a 2005 report described two patients who experienced rapid neurological deterioration after a fright. The disease is rare, with adult-onset cases accounting for about 15% of instances worldwide. A 2025 case report describes a 39-year-old man from Palestine who presented with a 7-month history of postural instability, imbalanced gait, and progressive lower extremity deterioration, along with ocular and sphincteric issues. Neurological examination found reduced cognitive function, spastic quadriparesis, hyperreflexia, bradykinesia, and shuffling gait. Routine laboratory tests of CSF, blood, and urine were normal. MRI showed periventricular white matter hyperintensities indicative of vanishing white matter leukoencephalopathy. 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. The coexistence of Parkinsonism complicated the diagnosis. No other treatments are reported in these abstracts for the inherited form of the disease. Separately, a 2004 study of treatment-induced leukoencephalopathy in primary CNS lymphoma examined five autopsied patients who died of leukoencephalopathy after successful lymphoma treatment. Median age at lymphoma diagnosis was 74 years; symptoms of neurotoxicity developed a median of one month after treatment completion, and median survival after neurotoxicity onset was 30 months. At autopsy no PCNSL was found. All had myelin and axonal loss, gliosis, pallor, spongiosis, and rarefaction of white matter; two had tissue necrosis, and one had fibrinoid necrosis of vessels. Four of five had atherosclerosis of large cerebral vessels and all had small vessel disease; two had recent strokes at autopsy. The authors concluded that treatment-induced leukoencephalopathy is not a late delayed consequence but can appear very early, and that vascular disease may be a component of the white matter injury.
A 2010 review of leukodystrophies with late disease onset notes that knowledge of metabolic and genetic basis is increasing, opening new treatment options such as enzyme replacement or cell-based therapies. It emphasises the importance of differentiating leukodystrophies from toxic, inflammatory, or vascular leukoencephalopathies. For vanishing white matter disease specifically, no cure currently exists. What is still missing are treatments that halt or reverse the progressive white matter loss, larger studies of adult-onset cases to clarify natural history and genetic heterogeneity, and clinical trials of any candidate therapy. The 2025 case report underscores that research on neurological disorders in Palestine is limited, and that diagnostic and therapeutic capabilities in the region need enhancement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2004 · 177 citations
Treatment-induced leukoencephalopathy in primary CNS lymphoma
AbstractBACKGROUND: Treatment-related leukoencephalopathy is the leading toxicity after successful treatment of primary CNS lymphoma (PCNSL). Its mechanism is poorly understood and there are no autopsy data available on such patients. METHODS: From a database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, the authors identified five autopsied patients who died of leukoencephalopathy. The authors reviewed their clinical records, MRI, and autopsy findings. RESULTS: The median age was 74 years (range 41 to 79) at PCNSL diagnosis. Symptoms of neurotoxicity developed a median of 1 month after treatment completion, and median survival was 30 months (range 22 to 68 months) after neurotoxicity onset. All had white matter hyperintensity on T2-weighted MRI, and two developed enhancing lesions 5 and 14 months following completion of treatment. At autopsy no PCNSL was identified. Myelin and axonal loss, gliosis, pallor, spongiosis, and rarefaction of the white matter were found in all; two patients had tissue necrosis that correlated with the enhancement on MRI, and one had fibrinoid necrosis of vessels. Four of the five patients had atherosclerosis of large cerebral vessels in the circle of Willis and all had small vessel disease; two had recent strokes at autopsy. CONCLUSIONS: Treatment-induced leukoencephalopathy is not a late delayed consequence of neurotoxic treatment but can be seen very early in some patients. Vascular disease may be a component of this white matter injury.
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.
Current Opinion in Neurology · 2010 · 55 citations
Leukodystrophies with late disease onset: an update
AbstractPURPOSE OF REVIEW: Knowledge of the metabolic and genetic basis of known and previously unknown leukodystrophies is constantly increasing, opening new treatment options such as enzyme replacement or cell-based therapies. This brief review highlights some recent work, particularly emphasizing results from studies in adulthood leukodystrophies. RECENT FINDINGS: Evidence from recent studies suggests increasing importance of metabolic dysfunctions, for example, in peroxisomal lipid metabolism or energy homeostasis, influencing axonal integrity and oligodendrocyte function and leading to white matter demyelination. In addition, diagnostic and therapeutic progress in metachromatic leukodystrophy, X-linked adrenoleukodystrophy, Krabbe diseases and other rare leukodystrophies with late onset are summarized. SUMMARY: Better understanding of leukodystrophies in neurological routine practice is of crucial importance for differentiating between other white matter diseases such as toxic, inflammatory or vascular leukoencephalopathies. Many leukodystrophies are particularly important to recognize because specific treatments already exist or are currently under investigation. The article also provides an overview of currently known leukodystrophies in adulthood.
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.
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.
