Long-term delivery of TPP1 enzyme to the eye and brain in CLN2

1. CLN2
Long-term delivery of TPP1 enzyme to the eye and brain in CLN2
Rebecca Whiting, Martin Katz, Ophthalmology, School of Medicine, University of Missouri
Acknowledgements:
Our thanks to collaborators on these projects including Joan Coates, Jacqueline Pearce, Jeffrey Bryan, Fred Wininger, Dawna Voekl, Dietrich Voelkman; to the Veterinary Post-docs Daniella Vansteenkiste, Baye
Williamson, Whitney Young; to Lani Castaner for assistance with all aspects of the project, and to the many students and dogs who made essential contributions to these studies. Financial support for these
projects was provided by the National Institutes of Health and the Knights Templar Eye Foundation.
INTRODUCTION
 CLN2 disease is caused by a lack of TPP1
enzyme, and supplying the enzyme to the
brain delays symptom progression
 Our laboratory is working to optimize
long-term delivery of the enzyme to the
brain and eye using a dog model of CLN2
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Normal Treated, CLN2 Untreated,
CLN2
#ofIncorrectChoices
Measure of Learning Ability
Treated, CLN2
Untreated, CLN2
TREATMENT PRESERVES VISUAL FUNCTION
TREATMENT PRESERVES COGNITIVE FUNCTION
take cells from
the bone marrow
Modify the cells
to produce TPP1
Inject the cells into the eye and brain where
they continue to produce TPP1 long term
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TREATED UNTREATED
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Normal Treated,
CLN2
Untreated,
CLN2
#ofIncorrectChoices
Measure of Learning Ability
METHODS
#ErrorsonCognitiveTest
Retina response to flash of light
Treatment prevents retina lesions
CONCLUSIONS
 A single injection of stem cells
into the eye can produce enough
TPP1 to preserve visual function
for 7 months or longer
 Preliminary results suggest that
treatment with the same cells will
preserve the brain long term
 We are making progress towards
a one-time curative treatment for
CLN2 disease.