Late Infantile Batten Disease
Martin L. Katz, Principal Investigator, University of Missouri School of Medicine, Mason Eye Institute, Columbia, MO 65212 E-mail: firstname.lastname@example.org
APPROACHES FOR TREATING CLN2
CLN2 Therapy Studies from the Neurodegenerative Diseases Research Laboratory
The cause of CLN2 is the lack of a protein
(enzyme) called tripeptidyl peptidase-1 (TPP1).
TPP1 is required for the breakdown of old damaged
proteins that cells need to get rid of.
If TPP1 is missing or defective the proteins and
fragments cannot be chopped up properly so they
aggregate and build up inside cells
The aggregates that accumulate in nerve cells in
CLN2 give off a golden yellow glow when slices of
tissue are viewed with fluorescence microscopy.
Brain Brain Spinal Cord
5It should be possible to cure CLN2 by
providing nerve and other cells with the
normal form of the TTP1 Protein.
Cells will take up TPP1 supplied to them.
The TPP1 protein will attach
to the surfaces of most cells.
After it attaches, the protein
is taken up into cells in small
vesicles. These vesicles
deliver the protein to a
specialized structure in the
cell called the lysosome. In
the lysosome the TPP1
enzyme carries out its
normal function of breaking
down old and damaged
4 TPP1 can be delivered widely throughout
the brain and spinal cord via the cerebral
Three Approaches for Delivering TPP1 to
the Cerebrospinal Fluid
Stem Cell Delivery
These approaches for therapy are being
tested in a Dachshund model for CLN2.
TPP1 is made by cells in culture, purified, and
then infused into the CSF. A clinical trial using
this approach is planned by BioMarin for 2013.
Copies of the TPP1 gene are made by cells in
culture, purified, and then infused into the
CSF. The genes are taken up by cells in the
brain and direct the cells to make and release
the TPP1 protein which then flows through the
Cultured stem cells are programmed to make
large amounts of the TPP1 protein. These cells
are implanted into the CSF where they take up
residence and release the protein.
A primary goal of the Neurodegenerative
Diseases Research Laboratory (NDRL) is to
develop a cure for the CLN2 form of Batten
Using a dog model we are evaluating 3
approaches to treatment: enzyme replacement
therapy; gene therapy; and stem cell therapy.
The cerebrospinal fluid
(CSF) is made in the brain
and circulates around the
entire brain and the spinal
The CSF flows through the
subarachnoid spaces where it
is in very close contact with
most structures and cells of the