DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronal ceroid lipofuscinosis 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 moduleNeuronal ceroid lipofuscinosis 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 neuronal ceroid lipofuscinosis 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.
What the evidence adds up to
Neuronal ceroid lipofuscinosis 5 is one of at least fourteen genetically distinct forms (CLN1 through CLN14) within the neuronal ceroid lipofuscinoses, a group of inherited neurodegenerative disorders that together constitute the most prevalent class of childhood neurodegenerative disease. These disorders are characterised by the intracellular accumulation of autofluorescent lipopigment (ceroid lipofuscin) in the brain, especially in neurons, and by progressive motor deterioration, cognitive decline, visual failure, epilepsy, cerebellar ataxia, and premature death. Clinical heterogeneity among the forms is explained by the different genes involved, and diagnosis is possible using enzymatic tests or direct sequencing of the corresponding genes.
The gene products for six of the eight forms known at the time had been discovered by 2003, and evidence pointed to functions for the CLN genes in the endosomal-lysosomal system, with neuron-specific roles for these proteins. A requirement for appropriate protein trafficking within neurons was suggested as a possible explanation for the profound and selective effects of these disorders upon the central nervous system. Animal models, including mouse and large animal models, had been developed, enabling comparative studies of progressive disease effects using morphological, biochemical, metabonomic, and microarray techniques.
In juvenile neuronal ceroid lipofuscinosis, a study using diffusion MR imaging in 14 affected children (mean age 9.6 years) and 14 controls found significant global and local structural brain connectivity network alterations. Global network properties were significantly reduced in the patient group, and local efficiency was decreased in the left supramarginal gyrus and temporal plane, with decreased strength in the right lingual gyrus. These network alterations correlated with disease severity and with areas related to symptomatology. A separate quantitative brain volumetric analysis noted that the clinical course and its variability across different NCL forms was still widely unknown at that time.
Therapeutic approaches in development include enzyme replacement therapy and gene transfer, but the 2012 review stated plainly that neuronal ceroid lipofuscinoses are still beyond remedy. What remains missing is sufficient knowledge of the natural history and clinical course of each specific form, including quantifiable endpoints that can be used in clinical trials. The efficacy of experimental treatments will depend on that knowledge, and no trial data for any drug in neuronal ceroid lipofuscinosis 5 specifically are reported in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Child Neurology · 2013 · 146 citations · open access
Classification and Natural History of the Neuronal Ceroid Lipofuscinoses
AbstractThe neuronal ceroid lipofuscinoses represent a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment (ceroid lipofuscin). Together, they represent the most prevalent class of childhood neurodegenerative disease. The neuronal ceroid lipofuscinoses encompass several distinct biological entities that vary in age of onset, specific neurologic phenotype, and rate of progression. In this review, we describe 9 major forms and present a classification scheme. Understanding the age of onset, clinical features, and natural history can inform rational diagnostics. Better knowledge of the natural histories of these disorders is necessary to shed light on the underlying pathobiology and to develop new therapeutics.
Neurological deterioration in late infantile neuronal ceroid lipofuscinosis
AbstractBACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL) is associated with progressive degeneration of the brain and retina starting in early childhood. METHODS: Thirty-two individual neurologic, ophthalmologic, and CNS imaging (MRI and MRS) assessments of 18 children with LINCL were analyzed. Disease severity was followed by two rating scales, one previously established but modified to solely assess the brain and exclude the retinal disease (modified Hamburg LINCL scale), and a newly developed scale, with expanded evaluation of the CNS impairment (Weill Cornell LINCL scale). RESULTS: For the 18 children, the Weill Cornell scale yielded a closer correlation with both age and time since initial clinical manifestation of the disease than did the modified Hamburg scale. There were no significant differences as a function of age or time since initial manifestation of the disease in the rating scales among the most frequent CLN2 mutations (G3556C, 56% of all alleles or C3670T, 22% of all alleles). Measurements of cortical MRS N-acetyl-aspartate content, MRI ventricular, gray matter and white matter volume, and cortical apparent diffusion coefficient correlated to a variable degree with the age of the children and the time since initial clinical manifestation of the disease. All imaging measurements correlated better with the Weill Cornell CNS scale compared to the modified Hamburg LINCL scale. CONCLUSION: The data suggest that the Weill Cornell late infantile neuronal ceroid lipofuscinosis (LINCL) scale, together with several of the MRI measurements, may be useful in the assessment of severity and progression of LINCL and for the evaluation of novel therapeutic strategies.
Current Opinion in Neurology · 2003 · 98 citations
Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis
AbstractPURPOSE OF REVIEW: The identification of genes mutated in the neuronal ceroid lipofuscinoses has accelerated research into the mechanisms that underlie these fatal autosomal recessive storage disorders, which are often referred to as Batten disease. This review summarizes progress in this field since October 2001, describing advances in cell biology, the characterization of new animal models of neuronal ceroid lipofuscinosis, and the impact of novel methodology to reveal insights into its pathogenesis. RECENT FINDINGS: Gene products for six of the eight forms of neuronal ceroid lipofuscinosis have now been discovered, and concerted efforts are underway to understand the normal biology of each gene product and how this may be altered by mutation. Several lines of evidence point to functions for the CLN genes in the endosomal-lysosomal system, and suggest neuron-specific roles for these proteins. Indeed, a requirement for appropriate protein trafficking within neurons may explain the profound and selective effects of these disorders upon the central nervous system. The development of mouse and large animal models has enabled comparative studies of the progressive effects of disease, including characterization by morphological and biochemical means supplemented by metabonomic and microarray techniques. SUMMARY: Insights into disease mechanisms are building a detailed profile of the impact of neuronal ceroid lipofuscinosis upon the brain. With the eventual aim of developing successful therapeutic strategies, it will be equally important to characterize the clinical progression of the disorder, and to identify quantifiable endpoints that can ultimately be used in clinical trials.
Cathepsin D deficiency causes juvenile-onset ataxia and distinctive muscle pathology
AbstractThe neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of neurodegenerative disorders with the most common phenotype consisting of early-onset progressive motor deterioration, cognitive decline, visual failure, epilepsy, cerebellar ataxia, and premature death.1 Acknowledgment: The authors thank the patients and families for help and support.
Oxford University Press eBooks · 2016 · 10 citations
Neuronal Ceroid Lipofuscinoses
AbstractNeuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative disorders beginning mainly in childhood, rarely in adults. They are characterized by the accumulation of autofluorescent lipopigments in brain, especially in neurons. Their clinical heterogeneity is now explained by the huge number of genes (from CLN1 to CLN14) involved in their pathogenesis. Their diagnosis is possible using enzymatic tests and/or direct sequencing of the corresponding genes. Different therapeutic approaches are in development for these diseases such as enzyme replacement therapy or gene transfer.
American Journal of Neuroradiology · 2019 · 8 citations · open access
Topological Alterations of the Structural Brain Connectivity Network in Children with Juvenile Neuronal Ceroid Lipofuscinosis
AbstractBACKGROUND AND PURPOSE: We used diffusion MR imaging to investigate the structural brain connectivity networks in juvenile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood. Although changes in conventional MR imaging are typically not visually apparent in children aged <10 years, we previously found significant microstructural abnormalities by using diffusion MR imaging. Therefore, we hypothesized that the structural connectivity networks would also be affected in the disease. MATERIALS AND METHODS: We acquired diffusion MR imaging data from 14 children with juvenile neuronal ceroid lipofuscinosis (mean ± SD age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean ± SD age, 11.2 ± 2.3 years; 7 boys). A follow-up MR imaging was performed for 12 of the patients (mean ± SD age, 11.4 ± 3.2 years; 8 boys). We used graph theoretical analysis to investigate the global and local properties of the structural brain connectivity networks reconstructed with constrained spherical deconvolution-based whole-brain probabilistic tractography. RESULTS: < .0003) decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus. CONCLUSIONS: We found significant global and local network alterations in juvenile neuronal ceroid lipofuscinosis that correlated with the disease severity and in areas related to the symptomatology.
Quantitative Brain Volumetric Analysis in Neuronal Ceroid Lipofuscinoses: A tool to precisely monitor disease progression
AbstractAims: Neuronal ceroid lipofuscinoses (NCLs) are still beyond remedy. The clinical course and its variability in the different NCL forms is widely unknown. The efficacy of experimental treatments presently being developed (gene therapy, enzyme replacement, stem cell transplantation) will have to be evaluated on the basis of sufficient knowledge of the clinical course.
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.
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