Enzyme replacement therapy attenuates disease progression in a canine model of late‐infantile neuronal ceroid lipofuscinosis (CLN 2 disease)
Open accessAbstract
Using a canine model of classical late‐infantile neuronal ceroid lipofuscinosis (CLN2 disease), a study was conducted to evaluate the potential pharmacological activity of recombinant human tripeptidyl peptidase‐1 (rhTPP1) enzyme replacement therapy administered directly to the cerebrospinal fluid (CSF). CLN2 disease is a hereditary neurodegenerative disorder resulting from mutations in CLN2, which encodes the soluble lysosomal enzyme tripeptidyl peptidase‐1 (TPP1). Infants with mutations in both CLN2 alleles develop normally but in the late‐infantile/early‐childhood period undergo progressive neurological decline accompanied by pronounced brain atrophy. The disorder, a form of Batten disease, is uniformly fatal, with clinical signs starting between 2 and 4 years of age and death usually occurring by the early teenage years. Dachshunds homozygous for a null mutation in the canine ortholog of CLN2 (TPP1) exhibit a similar disorder that progresses to end stage at 10.5–11 months of age. Administration of rhTPP1 via infusion into the CSF every other week, starting at approximately 2.5 months of age, resulted in dose‐dependent significant delays in disease progression, as measured by delayed onset of neurologic deficits, improved performance on a cognitive function test, reduced brain atrophy, and increased life span. Based on these findings, a clinical study evaluating the potential therapeutic value of rhTPP1 administration into the CSF of children with CLN2 disease has been initiated. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe is an easy surgical task and is commonly used to deliver drugs to the CNS.
“Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe of the brain is an easy surgical task, and is commonly used to deliver drugs to the CNS.”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [88]
Materials and Methods (rhTPP1 Formulation and Administration; page unavailable) describes a catheter placed in a lateral ventricle and used to infuse treatment into the CNS. It does not say the ventricle was targeted in the frontal lobe, that placement was an easy surgical task, or that this route is commonly used for CNS drug delivery. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sleat, D. E., DONNELLY, R. J., Lackland, H., Liu, C., Sohár, I., Pullarkat, R. K., & Lobel, P. (1997) · Science · doi:10.1126/science.277.5333.1802 · Cited by 581 · see citing works
Handbook of Veterinary Neurology
(2011) · Elsevier eBooks · doi:10.1016/c2009-0-60444-x · Cited by 291 · see citing works
The Neuronal Ceroid-Lipofuscinoses (Batten Disease)
Mole, S., & Haltia, M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-410529-4.00070-x · Cited by 220 · see citing works
Therapy for the mucopolysaccharidoses
Valayannopoulos, V., & Wijburg, F. A. (2011) · Lara D. Veeken · doi:10.1093/rheumatology/ker396 · Cited by 173 · see citing works
Chang, M., Cooper, J. D., Sleat, D. E., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.9 · Cited by 159 · see citing works
Passini, M. A., Dodge, J. C., Bu, J., Yang, W., Zhao, Q., Sondhi, D., Hackett, N. R., Kaminsky, S. M., Mao, Q., Shihabuddin, L. S., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2676-05.2006 · Cited by 154 · see citing works
Enzyme replacement therapy for lysosomal storage diseases
Lachmann, R. (2011) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e32834c20d9 · Cited by 143 · see citing works
Awano, T., Katz, M. L., O’Brien, D. P., Sohár, I., Lobel, P., Coates, J. R., Khan, S., Johnson, G. C., Giger, U., & Johnson, G. S. (2006) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2006.02.016 · Cited by 126 · see citing works
Self-citationGenetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses
Warrier, V., Vieira, M., & Mole, S. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.017 · Cited by 123 · see citing works
New Strategies for Enzyme Replacement Therapy for Lysosomal Storage Diseases
Grubb, J. H., Vogler, C. A., & Sly, W. S. (2010) · Rejuvenation Research · doi:10.1089/rej.2009.0920 · Cited by 79 · see citing works
Vuillemenot, B. R., Katz, M. L., Coates, J. R., et al. (2011) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2011.06.018 · Cited by 79 · see citing works
Self-citationTroponin as a marker of myocardiac damage in drug-induced cardiotoxicity
Adamcová, M., Štěrba, M., Šimůnek, T., Potáčová, A., Popelová, O., Mazurová, Y., & Geršl, V. (2005) · Expert Opinion on Drug Safety · doi:10.1517/14740338.4.3.457 · Cited by 78 · see citing works
Lin, L., & Lobel, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3570049 · Cited by 77 · see citing works
The Neuronal Ceroid Lipofuscinoses (Batten Disease)
(2012) · Oxford University Press eBooks · doi:10.1093/med/9780199590018.001.0001 · Cited by 59 · see citing works
Retinal Pathology in a Canine Model of Late Infantile Neuronal Ceroid Lipofuscinosis
Katz, M. L., Coates, J. R., Cooper, J. J., et al. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-1712 · Cited by 53 · see citing works
Self-citationButt, M. T. (2010) · Toxicologic Pathology · doi:10.1177/0192623310391679 · Cited by 47 · see citing works
Whiting, R. E. H., Narfström, K. L., Yao, G., et al. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.06.008 · Cited by 43 · see citing works
Kurachi, Y., Oka, A., Itoh, M., et al. (2001) · Acta Neuropathologica · doi:10.1007/s004010000321 · Cited by 34 · see citing works
2 Cellular pathology and pathogenic aspects of neuronal ceroid lipofuscinoses
Kida, E., Golabek, A. A., & Wisniewski, K. E. (2001) · Advances in genetics · doi:10.1016/s0065-2660(01)45003-6 · Cited by 33 · see citing works
Sanders, D. N., Kanazono, S., Wininger, F. A., et al. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00718.x · Cited by 29 · see citing works
Self-citationProgressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis
Fukumura, S., Saito, Y., SAITO, T. K., Komaki, H., Nakagawa, E., Sugai, K., Sasaki, M., Oka, A., & Takamisawa, I. (2011) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2011.04170.x · Cited by 25 · see citing works
The use of agalsidase alfa enzyme replacement therapy in the treatment of Fabry disease
Morel, C. F., & Clarke, J. T. R. (2009) · Expert Opinion on Biological Therapy · doi:10.1517/14712590902902296 · Cited by 24 · see citing works
Pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis
Whiting, R. E. H., Narfström, K. L., Yao, G., Pearce, J. W., Coates, J. R., Castaner, L. J., & Katz, M. L. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.10.006 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Study of Intraventricular Cerliponase Alfa for CLN2 Disease
Schulz, A., Ajayi, T., Specchio, N., de Los Reyes, E., Gissen, P., Ballon, D., Dyke, J. P., Cahan, H., Slasor, P., Jacoby, D., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1712649 · Cited by 489 · see citing works
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 169 · see citing works
Katz, M. L., Tecedor, L., Chen, Y., Williamson, B. G., Lysenko, E., Wininger, F. A., Young, W. M., Johnson, G. C., Whiting, R. E. H., Coates, J. R., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac6191 · Cited by 134 · see citing works
Self-citation
- Authors
- Katz, M. L., Coates, J. R., Sibigtroth, C. M., Taylor, J. D., Carpentier, M., Young, W. M., Wininger, F. A., Kennedy, D., Vuillemenot, B. R., & O'Neill, C. A.
- Affiliations
- University of Missouri (US)
- BioMarin (United States) (US)
- BioMarin Pharmaceutical Inc. Novato California
- Corresponding author
- Katz, Martin L.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2014-06-17
- Volume
- 92
- Issue
- 11
- Pages
- 1591-1598
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- PMC
- PMC4263309
- OpenAlex
- W1602997642
- Cited by
- 100
- References
- 23
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 14 · 2019: 12 · 2018: 6 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 4
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Batten Disease Support and Research Association (None)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- late infantile neuronal ceroid lipofuscinosis, CLN2 disease, tripeptidyl peptidase 1, enzyme replacement therapy, cerebrospinal fluid infusion, canine model, Dachshund, lysosomal storage disease, Batten disease, brain atrophy, neurodegeneration, cognitive function, disease progression
- MeSH terms
- Tripeptidyl-Peptidase 1, Aminopeptidases, Analysis of Variance, Animals, Brain, Cognition Disorders, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Disease Models, Animal, Dogs, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mutation, Neurologic Examination, Neuronal Ceroid-Lipofuscinoses, Recombinant Fusion Proteins, Survival Analysis, Disease Progression, Maze Learning, Enzyme Replacement Therapy, Serine Proteases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
