DeCure for Ceroid lipofuscinosis, neuronal, 6B (Kufs type)
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ceroid lipofuscinosis, neuronal, 6B (Kufs type) — 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 moduleCeroid lipofuscinosis, neuronal, 6B (Kufs type) 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 ceroid lipofuscinosis, neuronal, 6b (kufs type) 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
The abstracts describe neuronal ceroid lipofuscinosis (NCL), including the adult form known as Kufs disease. One 2005 case report describes a 38-year-old male with Klüver-Bucy syndrome as the initial manifestation of adult-type ceroid lipofuscinosis. Brain biopsy findings were characteristic of the disease. The patient had mixed clinical features of both type A (neuropsychiatric disorders) and type B (aphasia-apraxia-agnosia syndrome) of Kufs disease, and the authors note that adult-type ceroid lipofuscinosis is difficult to diagnose owing to the absence of peripheral biological markers, requiring histopathological confirmation.
A 2011 reference states that Kufs disease, the major adult form of NCL, is caused by mutations in CLN6, the same gene mutated in the variant late-infantile form. A 2003 review notes that gene products for six of the eight forms of NCL had been discovered, with evidence pointing to functions for the CLN genes in the endosomal-lysosomal system and neuron-specific roles for these proteins. The review also describes the development of mouse and large animal models for comparative studies of disease progression.
A 2014 abstract states that NCLs are a heterogeneous group of neurodegenerative disorders with a common phenotype of early-onset progressive motor deterioration, cognitive decline, visual failure, epilepsy, cerebellar ataxia, and premature death. A 2019 diffusion MR imaging study of 14 children with juvenile NCL (mean age 9.6 years) and 14 controls found significant global and local structural brain connectivity network alterations that correlated with disease severity and areas related to symptomatology. The study reported decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus.
No drug treatment is tested or mentioned in any of these abstracts. What is still missing for Kufs disease specifically are validated peripheral biomarkers, quantifiable clinical endpoints suitable for trials, and any therapeutic strategy that has been tested in patients. The 2003 review notes that characterising clinical progression and identifying quantifiable endpoints for clinical trials remains necessary.
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 · 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.
Current Opinion in Neurology · 2003 · 82 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.
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.
Síndrome de Klüver-Bucy como manifestación inicial de ceroidolipofuscinosis del adulto (enfermedad de Kufs)
AbstractAIMS: The purpose of this paper is to report the case of a patient with Kluver-Bucy syndrome caused by adult-type ceroid lipofuscinosis (Kufs' disease) and to review the literature dealing with the causes of this syndrome. CASE REPORT: A 38-year-old male examined because of behavioural changes and cognitive impairment. Brain biopsy findings were characteristic of adult-type ceroid lipofuscinosis. This patient fulfilled the criteria of Kufs' disease, since he had mixed clinical features belonging to both type A (neuropsychiatric disorders) and B (aphasia-apraxia-agnosia syndrome) of the disease. The initial symptoms included several clinical features of Klüver-Bucy syndrome (probable visual agnosia, apathy, increased sexual activity, lack of sexual inhibition, hypermetamorphopsia, increased oral behaviour and changes in dietary habits). CONCLUSIONS: Adult-type ceroid lipofuscinosis is an infrequent clinical entity that is difficult to diagnose owing to the absence of peripheral biological markers and the need to confirm such a diagnosis by means of a histopathological study.
Same gene, surprising difference: adult neuronal ceroid lipofuscinosis linked to CLN6, mutated in variant late-infantile form
AbstractReferences 1. Jalanko, A, Braulke, T. Neuronal ceroid lipofuscinoses. Biochim Biophys Acta 2009: 1793: 697– 709. 2. Abecasis, GR, Cherny, SS, Cookson, WO, Cardon, LR. Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002: 30: 97– 101. 3. Getty, AL, Pearce, DA. Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function. Cell Mol Life Sci 2011: 68: 453– 447. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6 Arsov et al. (2011) American Journal of Human Genetics 88(5): 566–573.
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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