0:04
What about other subtypes?
What about other genetic causes
and the 95% of
patients that don't
have a key autosomal
dominant genetic change
and have sporadic MND?
0:18
If you look in human
tissue, again,
you can find these
biochemical footprints of
free radical damage;
nitrotyrosine residues,
protein carbonyls, markers
of lipid oxidation,
markers of DNA damage.
8-hydroxy-2 deoxyguanosine
is a key marker
of oxidative damage to DNA.
You can find that in brain
and spinal cord tissue.
You can also find similar
biochemical changes
indicating the presence
of oxidative stress
in the cerebrospinal fluid,
the fluid that bathes the
brain and spinal cord,
and you can also find
biochemical evidence
of impaired antioxidant defence.
Reduced expression of the
peroxiredoxin enzyme,
reduced expression of NRF2,
and the downstream genes
controlled by that
transcription factor.
1:17
These are just some examples.
These are indices of
oxidative stress.
This is 8-hydroxy
deoxyguanosine.
You can see it's elevated in
ALS tissue compared to controls.
This is isoprostane, again,
elevated in MND patients
compared to controls.
Those oxidative stress
biomarkers are there in patients
with sporadic MND as well as
those with SOD1 mutations.
