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My name is Ian Coombs.
I am a researcher working
at University College London
in the Department
of Neuroscience,
Physiology and Pharmacology.
I've studied the pharmacology
and electrophysiology
of glutamate receptors
for the last 20 years.
Over the last couple of years
our groups worked
closely with CureGRIN,
which is a family led foundation
set up to drive research
into a newly identified family
of rare genetic
disorders that affect
the ionotropic
glutamate receptors.
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What I'm going to about is
give an introduction
into rare diseases,
how they're defined,
how they're diagnosed,
and also how we can afford
to develop drugs to treat them,
before talking about
my own subject.
I'll introduce the
glutamate receptors,
their structure,
their mechanisms of action,
and their roles in the brain.
Then I'll introduce
GRIA and GRIN disorder
which are these genetic diseases
affecting two classes
of glutamate receptor.
I'll be demonstrating the
numerous ways in which
genetic variation can
disrupt receptor function.
Finally, I'll talk about
therapy for GRI disorder,
including ongoing efforts
to identify precision
therapies both
through pharmaceutical
drugs and gene therapy.
1:09
Rare diseases are defined
from the UK Rare
Disease Framework
as any disease that affects
less than one in 2000
of the population.
In a country like the UK
with a population of
around 60 million,
if a disease affects
less than 30000 people
in the country,
that will class
as a rare disease
but of course many are
much rarer than that.
In fact, over 7000
different rare diseases
have been identified.
While the individual rare
diseases are of course rare,
collectively they're
not that rare.
They affect over five percent
of the population as a whole.
Research into these diseases
is certainly important
and 75% of them can
affect children,
and many are very serious
including even some
that are fatal.
These are commonly caused
by genetic factors.
These might be de novo changes,
so we are 50% our mother
and 50% our father,
but we are also
0.00000001% error.
Over the course of
millions of years
that counts as evolution.
But for a structure as
highly evolved as the brain,
de novo change is not
something that we want
to experience and very
commonly causes problems.
Not all of these
diseases are de novo
they can be inherited.
These can be directly inherited
from an affected individual
with a dominant disorder,
or if both parents have one
defective copy of a gene
that can come together
if the child has
both defective copies to
produce recessive disease.
That again is
obviously quite rare.
Another class of disease is
those found on the X chromosome.
Girls have two copies
of the X chromosome
so they have a backup copy,
they can tolerate
one deceptive copy
of the gene because
they have a backup.
Males on the other hand
only have one X chromosome.
If they get a damaged copy
either through de novo change
or inherited from the mother,
they can show signs of
X-linked disorders.
