bill mably for the brain channel and the
program we call on our mind I'm here
again with dr. Irene litte van professor
of neurosciences at UCSD and we're
talking about a disorder a movement
disorder that is her specialty she is
known nationally and internationally for
her contributions to understanding a
disorder that is hyphenated ER or
shortened to PSP Irene thanks for being
here tell us about PSP spell those words
out for us and and educate us about what
that disorder is and how we can try to
understand it and treat it thank you for
having me here
progressive supranuclear palsy
that's what PSP is the acronym for is a
disorder that occurs in the 60s it was
described initially by Steele Richardson
and of cesky in a set of seven patients
that have the disorder and they look
very characteristically similar and they
look at the pathology and they realize
that they have a pattern of disease that
they call progressive supranuclear palsy
because it is progressed a progressive
disease and because it occurs not only
that they have parkinsonism that is the
slowness the stiffness and the postural
instability that actually in this
disease is different than in Parkinson's
disease occurs very early but also they
have other features that are very
character
sticks of the disease one of them is the
difficulty moving their eyes up and down
and that is what we call super nuclear
gaze policy and that is part of the name
of the disease because the lesions are
not really where the nuclei that allows
the movement of the eyes are but above
that and that's what is above the
nucleus supranuclear and this difficulty
is particularly when looking up and down
eventually it occurs also when looking
to the sides patients also have
difficulties with speaking and also with
swallowing early in the course of the
illness and they also have some
executive dysfunction difficulties with
planning difficulties with sequencing
with abstract thought
pretty much the functions that defines
an executive person so this is rather
progresses rather rapidly in contrast to
what happens in Parkinson's disease and
patients unfortunately do not survive
longer than 10 years and in general less
than that and when you look at the
brains there is a type of protein that
exists normally in the brain that
constitutes part of the cell
particularly the walls of this of the
cell that is called tau that changes its
form and aggregates and so as it happens
in other diseases such as in Alzheimer's
and in Parkinson's disease this protein
misfold
changes its its format and again it has
been shown that in this disease as well
it goes
once that happens it allows the the cell
not to live so the cell dies and the
particles kind of go out of the cell or
before it's death if they get in contact
with neurons that are normal and they
make them sick by again making the
proteins miss fold so the miss folded
protein that is president one neuron is
communicated is released and
communicated to another neuron because
this protein called tau but it's not
normal tau it's not normally shaped it's
misshapen that's go ahead again what
about genetics in this disorder what do
we know about that
so in this is in that is different that
what happens in in other
neurodegenerative diseases there is not
a gene that you can say that really is
commute ated and that it goes from one
member of the family to another but this
gene tau is have some changes what we
call bali polymorphisms there are some
abnormalities of these of the seen that
occur in the majority of the patients
not all of pretty much all of them but
what I wanted to say actually is that it
also occurs in some normal people so
this kind of allows us to say that this
is kind of a susceptibility factor some
factor that by itself perhaps alone is
not sufficient to cause the disease but
it may be necessary and either other
genes or environmental factors may lead
to cause the disease we have studied the
environmental factors in in quite detail
we
at an NIH grant that allow us to have a
multicenter study that recruited 350
patients in 300 controls and we
investigated what were the possible
causes of the disease and what we found
is that there are environmental factors
that seem to be associated with the
disease
mostly what we were found that is
statistically significant is the
association with the use of well water
but there were other factors that were
there that did not get to to have
significance statistically but they were
very much probably aligned with the fact
that well water is related to pesticides
and is related to other toxins that the
majority of the patients did have an us
have lived in in farms or close to farms
and we also found that they may had work
in agricultural work as well as in
transportation and with metals
interesting enough there is a cluster of
patients that was just described in
France in a small town in which there
was a lot of toxins in that town and
this toxins may have been related to
metals and there were a lot of patients
with with this disease in the town that
were found to have progressive
supranuclear palsy even at autopsy so
there may be something there that we
don't have
full knowledge at this point but there
is a lot of growing evidence that
environment it has a role as well it's
exciting so so an environmental factor
and a genetic factor perhaps working
together to cause this protein to go to
run amok and I could imagine that the
misshapen protein fails to work normally
so that the neuron becomes sick partly
because of that but partly because
perhaps this protein then poisons the
Proteus stasis system the system that
keeps all the other proteins healthy are
those are those directions for research
in the field right now absolutely all
those are important areas of research
that are important for therapy as well
and this is what is really quite
exciting talk about the therapies that
are coming down the line so with the
idea of trying to contain this means
folded proteins going from one cell to
another treatments with antibodies are
coming to surface in fact we have two
studies at this point at UCSD with
antibodies against different parts of
tau it is unclear which is the part that
truly may be the one that is that may be
more important and leading to the MIS
folding of the protein but and that's
why there are more than one study that
is that is going on in one of them we
have enroll three patients and we are
starting with the other and this is
obviously very very exciting the
possibility of having therapies that
could truly slow the progression of the
disease is something that I pray that it
would happen and I'm so happy to see it
on absol alive and happening here at
UCSD so if those listening have concerns
or interests in this general topic but
specifically with PSP we'd encourage
them to contact dr. Littman and her
colleagues because not only are they
experts in diagnosis and management of
these patients but they're also engaged
in clinical trials
Irene thanks for being with us in
fantastic work thank you so much