This document discusses new perspectives on Batten disease and developing treatments. It summarizes that Batten disease affects multiple cell types in the brain and nervous system beyond just neurons. Developing treatments requires delivering therapies to broader areas of the brain and nervous system beyond mice models. The research aims to treat affected organs and develop new animal models and targets to more effectively treat the disease.

1. New perspectives on Batten disease CLN1, CLN2,
CLN3
and others…
Jon Cooper (PI), Hemanth Nelvagal (Wash U),
Martin Egeland, Allison Najafi, Ana Assis (UCLA), Charlott Repschlager (KCL)
Pediatrics, Washington University School of Medicine, St. Louis, MO.
There are billions of electrically
active nerve cells that
communicate via synapses
Our brains are very
complicated
& made up of many
different cells
Star shaped “astrocytes”
control the brain’s
environment
Small “microglia” act
as the brain’s
immune system
“oligodendrocytes”
Insulate the brain’s
“wiring”
The brain’s forgotten cells?
BUT there are many more glial cells that
work together to support them
They can no longer do their
normal jobs to
support nerve cells
They can even directly
harm nerve cells!
Glia have significant
problems in several
sorts of Batten disease
Make therapies work
better by treating
all types of cells
Yes, the lab did
just move (again)…
How to delivery
therapy to a
bigger brain?
Cln2
New larger animal models (CRISPR/CAS9)
Most of our
work is
done in mice
Cln1 sheep Cln3 pigs
but their brains
are very simple!
Moving beyond mice…
New targets for therapy?
Large and complex neurons
I
II
III
IV
V
VI
Inhibitory interneuronsThalamus
Some parts of the brain
are affected more
than others
It’s not just the brain that is affected
so is the spinal cord and brainstem
(Cln1, Cln2, Cln3, Cln6, Cln7 etc)
Targeting therapy to the right place is crucial
Brain
Spinal
cord
Gene therapy in Cln1 mice is MUCH
more effective if we do this
Other parts of the
nervous system are
affected in the rest
of the body in Cln1
Peripheral nervous system
(innervation of muscles)
Enteric nervous system
(innervation of gut)
Autonomic nervous system
(innervation of heart etc)
There appear to be problems in these target organs too. Which comes first?
We need to find ways to treat
these organs and nerves too
Think outside
The box (brain)…
This affects the way Battens mice can walk
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