1. A New and Effective method for intravenous Enyzyme replacement therapy:
Late Infantile Batten Disease
Yu Meng, David Sleat, Istvan Sohar, Peter Lobel. CABM, Rutgers University, Piscataway, NJ, 07076, lobel@cabm.rutgers.edu
INTRODUCTION
There is no effective
therapy for LINCL. Our
laboratory is evaluating
treatment regimens in
our mouse model to
provide proof-of-
principle for enzyme
replacement therapy
for LINCL.
KEY PROJECTS
1. We have developed a
new way of getting TPP1
from the bloodstream into
the brain. This is more
effective than any method
discovered to date for any
enzyme.
1. In principle, a non-
invasive enzyme
replacement therapy for
LINCL is a realistic
possibility.
1. These results provide
strong support for further
study of this remarkable
delivery method.
WHAT THIS MEANS
FOR THERAPY
Acknowledgements:
This work was supported in
part by a Johnson and
Johnson Focused Giving
Award and NIH R01 NS37918
to PL and a Batten Disease
Support and Research
Association fellowship to YM
Enzyme replacement
therapy has worked well
for some lysosomal storage
diseases. A synthetic form
of the protein that is
missing in patients is given
to patients, and it travels to
the lysosome and clears up
storage material.
1
4
Cerebral Cortex
LINCL
mouse
LINCL
mouse
treated
with TPP1
and
Peptide
6
LINCL is caused by the loss of a brain
enzyme, tripeptidyl peptidase 1. Enzyme
replacement therapy for LINCL is difficult
because the blood-brain barrier prevents
TPP1 administered into the blood
entering the brain. To date, there are no
good methods to beat the blood-brain
barrier.
2
We have developed a new way to
help TPP1 move from the
bloodstream into the brain. When
we inject mice with TPP1 and a
special peptide into the tail vein, we
can get 8-times higher than
normal activity in the brain.
When injected with the peptide,
the TPP1 enters the neurons
of the brain.
Intravenous treatment of mice with TPP1
alone doesn’t increase lifespan. However,
a single timepoint treatment with
TPP1 and the peptide extends the
lifespan of the LINCL mouse.
Treatment
5
3
Wild-type
mouse