DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neuronal ceroid lipofuscinosis 1 — screening already-approved drugs against its 4-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 1 maps to a 4-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 1 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
palmitoyl-protein thioesterase 1 (PPT1) — PPT1 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3GRO · 2.53 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
Neuronal ceroid lipofuscinosis 1 is one of at least fourteen genetically distinct forms of a group of inherited neurodegenerative disorders. The condition is characterised by the accumulation of autofluorescent lipopigments in the brain, particularly in neurons. Clinical features include early-onset progressive motor deterioration, cognitive decline, visual failure, epilepsy, cerebellar ataxia, and premature death. Diagnosis is possible using enzymatic tests or direct sequencing of the relevant genes. The gene products for six of the eight forms known in 2003 had been discovered, and evidence pointed to functions in the endosomal-lysosomal system, with neuron-specific roles that may explain the selective effects on the central nervous system.
Several therapeutic approaches have been proposed, including enzyme replacement therapy, gene therapy, stem cell therapy, small molecule pharmacotherapy, and diet modifications. Some of these therapies have demonstrated measures of success and progressed to human clinical trials. However, as of 2012, the neuronal ceroid lipofuscinoses were described as still beyond remedy. The clinical course and its variability across different forms was widely unknown, and the authors noted that the efficacy of experimental treatments would have to be evaluated on the basis of sufficient knowledge of the clinical course. A 2013 review stated that successful therapies in the future may necessitate the combination of two or more therapeutic modalities.
No abstract in this set reports quantitative outcomes such as survival or response rates in treated patients with neuronal ceroid lipofuscinosis 1. The 2014 report of cathepsin D deficiency causing juvenile-onset ataxia and distinctive muscle pathology is a separate form of NCL, not CLN1. What remains missing is sufficient natural history data to define quantifiable endpoints for clinical trials, therapies that can cross the blood-brain barrier and clear accumulated debris throughout the central nervous system, and the funding to move combination approaches from preclinical work into properly stratified human studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractJournal Article Presidential Address: Studies in the Neuronal Ceroid-Lipofuscinoses Get access Wolfgang Zeman, M.D. Wolfgang Zeman, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Neuropathology & Experimental Neurology, Volume 33, Issue 1, January 1974, Pages 1–12, https://doi.org/10.1097/00005072-197401000-00001 Published: 01 January 1974
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.
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.
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.
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.
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.
