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Canine Models for NCL Therapy Development
Martin L. Katz and Gary S. Johnson, School of Medicine and College of Veterinary Medicine, University of Missouri
Dog models for the neuronal ceroid lipofuscinoses (NCLs or
Batten disease) will be useful for evaluating the efficacy of
potential therapeutic interventions for treating these diseases.
The NCLs result from mutations in at least 13 different genes.
Different approaches to therapy are going to be required to
treat the different forms of NCL. Therefore, it will be important
to have suitable animal models for each of the forms of NCL.
A dog model for the CLN2 form of Batten disease played a
critical role in the development of an effective enzyme
replacement therapy currently being used to treat children with
this disorder. This has proven the utility of dog models in pre-
clinical studies required before approval can be obtained for
conducting human clinical trials. Our goal is to develop dog
models for each of the forms of NCL that can be used for
therapeutic intervention testing in preparation for conducting
human clinical trials.
Acknowledgements: This work was made possible by the many dog owners who contributed samples from their pets and the veterinarians who collected postmortem tissues. Numerous
research personnel contributed to the disease characterizations and mutation identifications. Among them are Tomoyuki Awano, Douglas Sanders, Dennis O’Brien, Liz Hansen, Fabiana
Farias, Jenny Guo, Douglas Gilliam, and Ana Kolicheski. Others who contributed to this work are listed on the laboratory website http://medicine.missouri.edu/neurodegenerativediseases/publications.php
Support for some of this work was provided by the BDSRA and the American Kennel Club Canine Health Foundation.
Establishing Canine NCL Models:
Naturally occurring canine NCLs identified to date: Significance:
• A Dachshund model for the CLN2 form of NCL
was used to demonstrate the efficacy of enzyme
replacement therapy that resulted in the recent
successful completion of human clinical trials of
this treatment in children by BioMarin
• Using this same model, gene therapy to the
central nervous system was also found to be
effective in treating this disease. This method of
treatment may be tested in children in the future.
• Currently we have preserved canine semen for the
CLN2 and CLN5 forms of Batten disease.
• We are screening dogs with the other forms of
NCL to obtain semen as a resource for breeding
• We also continue to search for dogs with different
forms of NCL that correspond to the remaining
forms of NCL. We have DNA samples from
several other dog breeds with NCL for which we
are seeking to causative mutation.
• We plan to establish a canine NCL models
resource center that will be able to generate dogs
affected with each of the forms of NCL.
• We developed a panel of biomarkers of NCL
disease progression in dogs that can be used in
testing for the therapeutic efficacy of treatments
using the dog models.