DeCure for Adult-onset autosomal dominant demyelinating leukodystrophy
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for adult-onset autosomal dominant demyelinating leukodystrophy — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdult-onset autosomal dominant demyelinating leukodystrophy maps to a 2-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 adult-onset autosomal dominant demyelinating leukodystrophy 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
aldehyde dehydrogenase 7 family member A1 (ALDH7A1) — ALDH7A1 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 naddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6O4C · 1.7 Å · ligand NICOTINAMIDE-ADENINE-DINUCLEOTIDE (NAD). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not describe any drug treatment for adult-onset autosomal dominant demyelinating leukodystrophy (ADLD). The 2021 Indian family report explicitly states the disorder has no known treatment. The 2017 Chinese family study identified an LMNB1 duplication as the cause but tested no therapy. The 1998 Norwegian family report describes a similar progressive central and peripheral demyelinating disease with no treatment mentioned. The 2008 review covers paediatric inflammatory demyelinating conditions such as multiple sclerosis and neuromyelitis optica, not ADLD, and discusses disease-modifying treatments for those paediatric disorders, not for adult-onset leukodystrophy.
The 2017 Chinese study used target exome sequencing and multiplex ligation-dependent probe amplification to diagnose LMNB1 duplication in a 52-year-old proband with autonomic abnormalities and pyramidal tract dysfunction; the family showed a trend of genetic anticipation. The 2021 Indian study used real-time PCR to detect LMNB1 duplication across four generations and emphasised the disorder’s clinical similarity to multiple sclerosis but with characteristic symmetrical leukodystrophy on MRI. The 1998 Norwegian family reported five affected members with onset between 30 and 70 years, sensory loss, muscle deterioration, distal weakness, unsteady gait, dysarthria, and in five of nine second-generation members, strokes and mental deterioration; cerebrospinal fluid protein was increased in seven subjects, and neuroimaging showed widespread white matter disorder.
No trial, no drug, no intervention of any kind is tested or proposed for ADLD in these abstracts. The 2021 paper notes the disorder is rare and has no known treatment. What is missing is any preclinical or clinical drug development effort, any funding for such work, any trial design, and any patient stratification strategy for this genetically defined but therapeutically orphaned disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2008 · 38 citations
Epidemiology, immunopathogenesis and management of pediatric central nervous system inflammatory demyelinating conditions
AbstractPURPOSE OF REVIEW: Pediatric inflammatory demyelinating central nervous system diseases comprise monofocal and potentially monophasic disorders like optic neuritis and transverse myelitis, the multifocal, self-limiting disorder of acute disseminated encephalomyelitis, and multifocal chronic diseases like relapsing neuromyelitis optica and multiple sclerosis. This review discusses characteristics of these disorders with focus on epidemiology and treatment of acute disseminated encephalomyelitis, neuromyelitis optica and multiple sclerosis. RECENT FINDINGS: An international consensus group very recently defined diagnostic criteria for pediatric multiple sclerosis and acute disseminated encephalomyelitis. Immunological studies on pediatric inflammatory demyelinating disorders revealed possible disease-related humoral and T-cellular pathomechanisms. The recently identified biomarker for neuromyelitis optica, aquaporin-4-autoantibody, was detected in children with relapsing neuromyelitis optica with a similar frequency as in adult neuromyelitis optica patients. Clinically relevant, there is growing evidence that disease-modifying treatments are well tolerated and effective in the pediatric age group also. SUMMARY: Recent studies on pediatric inflammatory demyelinating central nervous system diseases have contributed to current awareness that these disorders are not restricted to the adult age group, and that some of them carry an unfavorable long-term prognosis. Growing knowledge will hopefully enable more timely diagnoses and more specifically tailored therapies in the near future, with the goal of improving outcomes in this young patient group.
Frontiers in Molecular Neuroscience · 2017 · 18 citations · open access
An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis
AbstractAutosomal dominant adult-onset demyelinating leukodystrophy (ADLD) is a very rare neurological disorder featured with late onset, slowly progressive central nervous system demyelination. Duplication or over expression of the lamin B1 (LMNB1) gene causes ADLD. In this study, we undertook a comprehensive clinical evaluation and genetic detection for a Chinese family with ADLD. The proband is a 52-year old man manifested with autonomic abnormalities, pyramidal tract dysfunction. MRI brain scan identified bilateral symmetric white matter hyper-intensities in periventricular and semi-oval white matter, cerebral peduncles and middle cerebellar peduncles. The proband has a positive autosomal dominant family history with similar clinical manifestations with a trend of genetic anticipation. In order to understand the genetic cause of the disease in this family, target exome capture based next generation sequencing has been done, but no causative variants or possibly pathogenic variants has been identified. However, Multiplex ligand-dependent probe amplification(MLPA) showed whole duplication of LMNB1 gene which is co-segregated with the disease phenotype in this family. This is the first genetically confirmed LMNB1 associated ADLD pedigree from China.
Progressive Central and Peripheral Demyelinating Disease of Adult Onset in a Norwegian Family
AbstractOBJECTIVE: To describe the clinical features of a Norwegian family with a combined central and peripheral demyelinating disease. DESIGN: Multiple case report. SUBJECTS AND MATERIALS: Three generations of a Norwegian family. Medical records were available for all 9 members of the second generation and 5 affected members in the third generation. RESULTS: At least 5 members had clinical features, neuroimaging findings, and electrophysiologic signs indicating a chronic progressive disorder affecting both the central and peripheral nervous systems. The clinical symptoms developed between the ages of 30 and 70 years in affected family members, who gradually developed sensory loss, muscle deterioration, and distal weakness in all extremities, unsteady gait, and dysarthria. Five of 9 persons in the second generation had strokes and experienced mental deterioration. The initial stroke episodes were recognized between the ages of 54 and 68 years, and death occurred between the ages of 62 and 75 years. In 7 subjects, cerebrospinal fluid protein levels were increased, and in 5 agar gel electrophoresis indicated blood-brain barrier dysfunction. Seven family members had neuroimaging signs of a widespread white matter disorder. In 4 subjects, neurophysiological investigations indicated a polyneuropathy, and in 3 subjects, results from a sural nerve biopsy showed a demyelinating neuropathy. There was no evidence of co-inheritance with genetic markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (19p), PMP22 (17q), APP (21q), CMTX1 (Xq), or PLP (Xq). CONCLUSIONS: Progressive central and peripheral demyelinating disease seems to be a distinct type of hereditary adult-onset demyelinating disorder affecting both the peripheral and central nervous systems. Its exact nature remains unknown.
Annals of Indian Academy of Neurology · 2021 · 3 citations · open access
LMNB1 Duplication-Mediated Autosomal Dominant Adult-Onset Leukodystrophy in an Indian Family
AbstractAutosomal dominant leukodystrophy is an adult onset neurodegenerative disorder presenting with progressive symptoms of ataxia and autonomic dysfunction in fourth or fifth decade in life. It has clinical similarity with multiple sclerosis, but shows characteristic magnetic resonance imaging findings of diffuse bilaterally symmetrical leukodystrophy which can distinguish this disorder. It is a rare disorder with no known treatment till date, and has never been described from the Indian subcontinent. We present an Indian family with autosomal dominant adult-onset demyelinating leukodystrophy with multiple members affected over four generations, and demonstrate a cheap and accurate molecular method of real-time polymerase chain reaction to detect the LMNB1 gene duplication, which is the genetic basis of this devastating disorder.
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.
