DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronal ceroid lipofuscinosis 13 — 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 13 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 13 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
cathepsin F (CTSF) — CTSF 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 3-benzenesulfonyl-1-propyl-allylcarbamoyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1M6D · 1.7 Å · ligand 4-MORPHOLIN-4-YL-PIPERIDINE-1-CARBOXYLIC ACID [1-(3-BENZENESULFONYL-1-PROPYL-ALLYLCARBAMOYL)-2-PHENYLETHYL]-AMIDE (MYP). Experimental structure, not a prediction.
What the evidence adds up to
Neuronal ceroid lipofuscinosis 13 is not mentioned in any of the provided abstracts. The abstracts cover CLN2 disease (with a 2021 case series of 8 Colombian patients treated with cerliponase alfa), juvenile neuronal ceroid lipofuscinosis (14 children studied with diffusion MRI in 2019), CLN11 (9 new cases from Latin America reported in 2024), and general reviews of the NCLs from 2013 and 2016. No abstract discusses CLN13, its genetics, its clinical features, or any treatment for it.
For CLN2, the 2021 case series of 8 patients found that after starting cerliponase alfa, no patient declined more than 2 points on the Hamburg, Weill Cornell and CLN2 clinical assessment scale during up to 24 months of follow-up. The authors report no serious adverse events. Five of the 8 patients had an atypical phenotype, with symptom onset at a mean of 48 months versus 24 months for the classical form. A novel mutation c.1438G>A was found in two siblings. The study is a small, uncontrolled case series from a single country.
For juvenile NCL (CLN3), the 2019 diffusion MRI study of 14 children found significantly decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus, compared to 14 controls. These network alterations correlated with disease severity. The study does not report any treatment or clinical outcome.
For CLN11, the 2024 retrospective study of 9 patients from 9 unrelated families reports age of onset between 3 and 17 years, with visual impairment, cerebellar ataxia, seizures, myoclonus, and cognitive decline as common findings. Most patients could walk unassisted after an average of 14.2 years from disease onset. One patient had a previously unreported finding of cervical, perioral, and tongue myoclonus. The authors describe a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant. No treatment is discussed.
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.
Molecular Genetics and Metabolism Reports · 2021 · 12 citations · open access
“Real world effectiveness of cerliponase alfa in classical and atypical patients. A case series”
AbstractINTRODUCTION: gene, with secondary enzyme deficiency. In classical phenotypes, initial symptoms include seizures and delayed language development between 2 and 4 years of age. This article describes the presentation of CLN2 disease in a cohort of Colombian patients, as well as the impact of treatment on the course and progression of the disease. METHODS: Case series report of 8 patients with a confirmed diagnosis of neuronal ceroid lipofuscinosis treated with cerliponase alfa who remained on clinical and paraclinical follow-up for up to 24 months before and after treatment. RESULTS: An atypical phenotype, associated with initial symptoms and late diagnosis, was present in 5/8 patients. The most frequent symptoms were seizures and developmental delay, with age of onset at 24 months (classical phenotype) and 48 months (atypical phenotype). A novel mutation (c.1438G > A) was found in two siblings. All of the patients received cerliponase alfa, and there were no serious adverse events. No decline in the clinical status greater than 2 points on Hamburg, Weill Cornell and CNL2 clinical assessment scale was observed during follow-up after treatment initiation. CONCLUSION: This is the first case series reported for neuronal ceroid lipofuscinosis patients in Colombia. In contrast with other reports, the majority of cases reported here displayed an atypical phenotype. Our study highlights the importance of early diagnosis and timely initiation of therapy, which is a feasible therapy, well tolerated by patients and accepted by caregivers in this country, generating a positive impact in the quality of life of CLN2 patients and on disease outcome.
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.
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.
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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