An update on the progress of preclinical models for guiding therapeutic management of neuronal ceroid lipofuscinosis

ABSTRACT Introduction: The neuronal ceroid lipofuscinoses (NCLs) are a group of pediatric inherited neurodegenerative disorders affecting children and young adults. All forms of NCL are fatal and with no curative therapies available there is a pressing need to model their pathology in biological model systems to enable the systematic and rigorous testing of preclinical therapies. Areas covered: This article discusses and provides an update on the recent advances in modelling NCL disease pathology in various different model systems and their relevance to testing preclinical therapies so as to ensure optimal translation into human patients. The research articles discussed here were curated from PubMed (Last accessed-12.4.19) and Google Scholar (Last access-12.4.19) databases. Expert opinion: Both in vitro and in vivo biological model systems have been established for various forms of NCL. These have informed us about pathophysiology, revealed novel therapeutic targets, and provided landmarks of disease progression against which to test potential therapies. Studying NCL pathology across different species has been very informative regarding where therapies need to be delivered with an increasing focus on disease outside the brain. Testing such therapies in animal models of increasing complexity has allowed the translation of more efficacious therapies for clinical trials.

• Publication year

  2019

• Venue

  Expert Opinion on Orphan Drugs

• Publication date

  2019-12-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/21678707.2019.1703672
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Pharmacological approaches to tackle NCLs.

  2020cited by this paper
• Combined Anti-inflammatory and Neuroprotective Treatments Have the Potential to Impact Disease Phenotypes in Cln3−/− Mice

  2019cited by this paper
• ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis

  2019cited by this paper
• A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome motility and impaired cell survival.

  2019cited by this paper
• Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses

  2019cited by this paper
• CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease)

  2019cited by this paper
• Recent Insights into NCL Protein Function Using the Model Organism Dictyostelium discoideum

  2019cited by this paper
• Therapeutic landscape for Batten disease: current treatments and future prospects

  2019cited by this paper
• Autophagy–lysosome pathway alterations and alpha-synuclein up-regulation in the subtype of neuronal ceroid lipofuscinosis, CLN5 disease

  2019cited by this paper
• Transcriptional Regulation of Autophagy: Mechanisms and Diseases

  2019cited by this paper
• Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses

  2019cited by this paper
• Characterization of a novel porcine model of CLN3-Batten disease

  2019cited by this paper
• Batten Disease

  2019cited by this paper
• Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model

  2019cited by this paper
• Neuronal ceroid lipofuscinosis related ER membrane protein CLN8 regulates PP2A activity and ceramide levels.

  2019cited by this paper
• Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease

  2019cited by this paper
• Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis.

  2019influential reference
• A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs.

  2019cited by this paper
• Paroxysmal sympathetic hyperactivity in Juvenile neuronal ceroid lipofuscinosis (Batten disease).

  2018cited by this paper
• CLN8 is an ER cargo receptor that regulates lysosome biogenesis

  2018cited by this paper
• Discovery of a CLN7 model of Batten disease in non-human primates

  2018cited by this paper
• Study of Intraventricular Cerliponase Alfa for CLN2 Disease

  2018cited by this paper
• Secretion and function of Cln5 during the early stages of Dictyostelium development.

  2018cited by this paper
• Immunomodulation with minocycline rescues retinal degeneration in juvenile neuronal ceroid lipofuscinosis mice highly susceptible to light damage

  2018cited by this paper
• Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses

  2018cited by this paper
• Neuronal Ceroid Lipofuscinoses: Connecting Calcium Signalling through Calmodulin

  2018cited by this paper
• Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.

  2018cited by this paper
• Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses

  2018cited by this paper
• Natural history data for childhood neurodegenerative disease.

  2018cited by this paper
• Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis

  2018cited by this paper
• Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells.

  2018cited by this paper
• Gene Therapy Approaches to Treat the Neurodegeneration and Visual Failure in Neuronal Ceroid Lipofuscinoses.

  2018cited by this paper
• Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery

  2018cited by this paper
• Loss of Cln3 impacts protein secretion in the social amoeba Dictyostelium.

  2017cited by this paper
• Decreased sensitivity of palmitoyl protein thioesterase 1-deficient neurons to chemical anoxia

  2017cited by this paper
• Long-term safety and efficacy of intracerebroventricular enzyme replacement therapy with cerliponase alfa in children with CLN2 disease: interim results from an ongoing multicenter, multinational extension study

  2017cited by this paper
• Bridging the gap: large animal models in neurodegenerative research

  2017cited by this paper
• Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy

  2017cited by this paper
• Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression

  2017cited by this paper
• Progress toward Fulfilling the Potential of Immunomodulation in Childhood Neurodegeneration?

  2017cited by this paper
• mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases

  2017cited by this paper
• Synergistic effects of treating the spinal cord and brain in CLN1 disease

  2017cited by this paper
• Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3) in the first decade of life

  2017cited by this paper
• Yeast as a model for the identification of novel survival-promoting compounds applicable to treat degenerative diseases.

  2017cited by this paper
• Cerliponase Alfa: First Global Approval

  2017cited by this paper
• Gemfibrozil, food and drug administration‐approved lipid‐lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis

  2017cited by this paper
• High-content drug screening for rare diseases

  2017cited by this paper
• Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of Neuronal Ceroid Lipofuscinosis

  2017cited by this paper
• Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

  2017cited by this paper
• Translating preclinical models of neuronal ceroid lipofuscinosis: progress and prospects

  2017cited by this paper
• Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo

  2017cited by this paper
• A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies

  2017cited by this paper
• Management Strategies for CLN2 Disease.

  2017cited by this paper
• in vivo localization of the neuronal ceroid lipofuscinosis proteins, CLN3 and CLN7, at endogenous expression levels

  2017cited by this paper
• Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia

  2016cited by this paper
• Efficacy of phosphodiesterase‐4 inhibitors in juvenile Batten disease (CLN3)

  2016cited by this paper
• Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3)

  2016cited by this paper
• An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep

  2016cited by this paper
• A High-Throughput, Multi-Cell Phenotype Assay for the Identification of Novel Inhibitors of Chemotaxis/Migration

  2016cited by this paper
• Induced pluripotent stem cell technology: a decade of progress

  2016cited by this paper
• Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression

  2016cited by this paper
• A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death Inhibitors

  2016cited by this paper
• Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

  2016cited by this paper
• Lysosomal dysfunction disrupts presynaptic maintenance and restoration of presynaptic function prevents neurodegeneration in lysosomal storage diseases

  2016cited by this paper
• Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

  2016cited by this paper
• Juvenile neuronal ceroid lipofuscinosis (Batten disease): current insights

  2016cited by this paper
• Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7.

  2016cited by this paper
• Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology

  2015cited by this paper
• Activation of Peroxisome Proliferator-activated Receptor α Induces Lysosomal Biogenesis in Brain Cells

  2015cited by this paper
• Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis.

  2015influential reference
• Toward stem cell-based phenotypic screens for neurodegenerative diseases

  2015cited by this paper
• AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease

  2015influential reference
• Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis.

  2015cited by this paper
• Genetics of the neuronal ceroid lipofuscinoses (Batten disease).

  2015cited by this paper
• A Case-controlled Investigation of Pain Experience and Sensory Function in Neuronal Ceroid Lipofuscinosis

  2015cited by this paper
• Finding the most appropriate mouse model of juvenile CLN3 (Batten) disease for therapeutic studies: the importance of genetic background and gender

  2015cited by this paper
• New Zebrafish Models of Neurodegeneration

  2015cited by this paper
• Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network.

  2015cited by this paper
• The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.

  2015cited by this paper
• Tissue‐specific variation in nonsense mutant transcript level and drug‐induced read‐through efficiency in the Cln1 R151X mouse model of INCL

  2015cited by this paper
• Human NCL Neuropathology.

  2015cited by this paper
• Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function*

  2015cited by this paper
• Towards a new understanding of NCL pathogenesis.

  2015cited by this paper
• Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier.

  2015cited by this paper
• Cell biology of the NCL proteins: What they do and don't do.

  2015cited by this paper
• Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study.

  2014cited by this paper
• Partial Correction of the CNS Lysosomal Storage Defect in a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis by Neonatal CNS Administration of an Adeno-Associated Virus Serotype rh.10 Vector Expressing the Human CLN3 Gene

  2014cited by this paper
• Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum

  2014cited by this paper
• Animal models in translational medicine: Validation and prediction

  2014cited by this paper
• Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway.

  2014cited by this paper
• Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease)

  2014cited by this paper
• Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease.

  2014cited by this paper
• An Anti-Neuroinflammatory That Targets Dysregulated Glia Enhances the Efficacy of CNS-Directed Gene Therapy in Murine Infantile Neuronal Ceroid Lipofuscinosis

  2014cited by this paper
• A Murine Model of Variant Late Infantile Ceroid Lipofuscinosis Recapitulates Behavioral and Pathological Phenotypes of Human Disease

  2013cited by this paper
• Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease).

  2013cited by this paper
• Human pathology in NCL.

  2013cited by this paper
• Phenotypic screens as a renewed approach for drug discovery.

  2013cited by this paper
• Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited α-synuclein accumulation and age-dependent sensorimotor deficits.

  2013cited by this paper
• NCL diseases - clinical perspectives.

  2013influential reference
• Classification and Natural History of the Neuronal Ceroid Lipofuscinoses

  2013cited by this paper

• No citing papers are available for this paper.