DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronal ceroid lipofuscinosis 11 — 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 11 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 11 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 neuronal ceroid lipofuscinoses are a group of fatal autosomal recessive storage disorders that represent the most prevalent class of childhood neurodegenerative disease. They are characterised by neurodegeneration and intracellular accumulation of auto-fluorescent lipopigment. The disorders vary in age of onset, neurologic phenotype, and rate of progression. By 2013, 14 known NCLs had been described. Gene products for six of the eight forms had been discovered by 2003, with evidence pointing to functions in the endosomal-lysosomal system and neuron-specific roles for the CLN proteins. A 2019 study using diffusion MR imaging in 14 children with juvenile neuronal ceroid lipofuscinosis (mean age 9.6 years) and 14 controls found significant global and local structural brain connectivity network alterations that correlated with disease severity.
CLN11 is a very rare form, reported in only 13 unrelated families before 2024. A 2024 retrospective observational study identified 9 additional CLN11 patients from 9 unrelated Latin American families. Age of onset ranged from 3 to 17 years. The most common findings were visual impairment, cerebellar ataxia, seizures, myoclonus, and cognitive decline. One patient had a previously unreported finding of cervical, perioral, and tongue myoclonus. Most patients could walk unassisted after an average of 14.2 years (SD 4.76 years) from disease onset, suggesting relatively slow progression. The study identified a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant in the GRN gene.
Various treatment modalities have been proposed, including enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy, and diet modifications. Some therapies have shown measures of success and progressed to human clinical trials. However, challenges include the blood-brain barrier preventing access to the central nervous system and the need to remove accumulated debris throughout the CNS. The 2013 review noted that successful therapies may require combining two or more modalities. What remains missing are well-characterised quantifiable endpoints for clinical trials, better understanding of natural history across all subtypes, and evidence from adequately powered controlled trials for any specific intervention. No drug is mentioned in these abstracts as having demonstrated efficacy in CLN11 or any other NCL form.
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.
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.
Expert Opinion on Orphan Drugs · 2013 · 9 citations
Advances in the treatment of neuronal ceroid lipofuscinosis
AbstractIntroduction: Neuronal ceroid lipofuscinoses (NCL) represent a class of neurodegenerative disorders typically characterized by cognitive and visual impairment, seizures, deterioration of motor skills and early mortality. There has been increased interest in developing therapies directed towards slowing the progression, and possibly preventing and reversing the impact of these disorders. Despite many challenges, including the presence of the blood–brain barrier which prevents access to the central nervous system (CNS) and the need to markedly remove accumulated debris throughout the CNS, many treatment modalities have been proposed, including enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy and diet modifications. Some therapies have demonstrated measures of success, and these have progressed to human clinical trials. Continued development of current therapies and discovery of newer approaches will be essential for success. Areas covered: The reader will be introduced to the 14 known NCLs, the current approach to therapies, the evidence for efficacy and the challenges to success both at the pre-clinical and clinical stage. This review corresponds to the literatures covering the years from 1968 to mid-2013. Expert opinion: Much progress has been made in the classification of this family of neurologic diseases, including the genetic basis and functional outcomes which have led to the evaluation of several therapeutic interventions. These include enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy and diet modifications, each of which has associated pros and cons. Successful therapies in the future may necessitate the combination of two or more therapeutic modalities.
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.
Genetics in Medicine · 2024 · 5 citations · open access
Further description of the phenotypic spectrum of neuronal ceroid lipofuscinosis type 11
AbstractPURPOSE: Ceroid lipofuscinosis type 11 (CLN11) is a very rare disease, being reported in only 13 unrelated families so far. Further reports are necessary to comprehend the clinical phenotype of this condition. This article aims to report 9 additional cases of CLN11 from 9 unrelated Latin American families presenting with relatively slow disease progression. METHODS: This was a retrospective observational study including patients with CLN11. Patients were identified through an active search for granulin precursor gene (GRN) pathogenic variants across the entire database of next-generation sequencing of a commercial laboratory and by contacting attending physicians to check for clinical and radiologic findings compatible with a neuronal ceroid lipofuscinosis phenotype. RESULTS: Nine CLN11 patients from unrelated families were evaluated. Age of onset varied between 3 to 17 years. The most common findings were visual impairment, cerebellar ataxia, seizures, myoclonus, and cognitive decline. One patient had a previously unreported finding of cervical, perioral, and tongue myoclonus. Most of the patients were able to walk unassisted after an average of 14.2 years (SD 4.76 y) from disease onset. CONCLUSION: We describe 9 new cases of a very rare type of neuronal ceroid lipofuscinosis (CLN11) from Latin America with a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant. Our findings suggest that a slowly progressive neuronal ceroid lipofuscinosis might be a clue for the diagnosis of CLN11.
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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