Long-term delivery of TPP1 enzyme in the canine model of CLN2

1. CLN2
Long-term delivery of TPP1 enzyme in the canine model of CLN2
Rebecca Whiting, Martin Katz, Ophthalmology, School of Medicine, University of Missouri
http://medicine2.missouri.edu/neurodegenerativediseases/
LONG TERM TREATMENT AFTER A SINGLE INJECTION
 Preliminary results suggest that the same cells will be
successful in treating the brain long term
CONCLUSIONS
 Stem cell delivery of TPP1 enzyme shows potential for providing TPP1 long-term after a single injection.
 We are making progress towards the goal of a one-time curative treatment for CLN2
INTRODUCTION
 Our lab continues working to optimize
long-term delivery of TPP1 to the brain
and eye using a dog model of CLN2.
We are also
beginning to work on
supplying TPP1 to the
rest of the body.
 A single injection of stem cells into the eye can
produce enough TPP1 to preserve function and
structure of the retina for 7 months or longer
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
1 2 3
Stem Cell Delivery of TPP1
Acknowledgements: Our thanks to collaborators on these projects including Joan Coates, Jacqueline Pearce, Juri Ota-Kuroki, Jeffrey Bryan, Fred Wininger, Dawna Voelkl, Dietrich
Volkmann; to the Veterinary Postdocs Stefanie Lim, Katherine Bibi, 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.
Funding for these studies was provided by Noah’s Hope/Hope 4 Bridget, Drew's Hope, NIH National Eye Institute, Knights Templar Eye Foundation, and Washington University ICTS.
TPP1-expressing cells survived
in the brain for 7 months after
implantation and were still
expressing a marker protein
Dogs that had
TPP1-expressing
cells injected into
the cerebrospinal
fluid retained
cognitive ability
longer than
untreated dogs
Treatment with
TPP1-expressing
cells prevented
retina detachment
lesions
Untreated Treated
(Measureofretinafunction)
 Vision loss in CLN2
results from
degeneration of both
the retina and the
brain, so vision
preservation will
require treatment of
both tissues.
 When lifespan was
extended in dogs that
received brain
treatment, disease
became apparent in
other organs outside of
the nervous system,
such as heart and liver.
A cure for CLN2 disease
will require treatment
for the whole body.