Novel therapies for the prevention of cardiovascular diseases

Novel therapies for the prevention of cardiovascular diseases


Cardiovascular disease is killing us. It is
the leading cause of death in the Western World and that includes right here in Australia.
If you were to go up to Stirling Highway and take a look at the UWA clock tower everytime
that minute hand moves 12 minutes, one Australian dies from cardiovascular disease. Genetic mutations in the contractile proteins
in the heart contribute to this burden. Contractile proteins are important in the heart as they
allow it to expand and contract and therefore maintain the heartbeat. Mutations to this
protein mean that the heart can no longer beat properly and this leads to the development
of an enlarged heart. Strikingly one in 200 of the general population have these mutations
with the outcome being the development of sudden cardiac death. Sadly this is the leading
cause of death in the young, including in children and young, healthy athletes. Next
I will show you a video of a young healthy athlete with one of these gene mutations.
While on the soccer field, this young man collapses, he’s having a cardiac arrest.
Fortunately due to a defibrillator that is implanted in his chest, he’s immediately
administered a shock that kick starts his heart back into rhythm and he survives. However
this is not the case for most people with these mutations. Most people with these mutations
don’t actually know they have the mutation until they collapse in cardiac arrest and
the outcome is fatal. So, how do these gene mutations result in
sudden cardiac death? What is the missing link? Well using technology where we can assess
the function of individual heart cells on a microscopic level we find that heart cells
from healthy hearts contain a channel in their cell membrane. This channel is important because
it initiates the heart beat much like the starter motor in a car. They are directly
connected to these scaffolding proteins and these scaffolding proteins are directly connected
to mitochondria and, in the heart, mitochondria are the powerhouses of the cell and they are
responsible for producing the energy required to maintain the heartbeat. So the channel
and mitochondria communicate with each other to maintain a normal, beating heart. In cells
from enlarged hearts, these scaffolding proteins are severely disrupted. This results in a
communication breakdown between the channel and mitochondria resulting in an overproduction
of energy. With this, the heart works harder and since the heart is a muscle, with increased
work, it gets bigger to the point where it can no longer function – and it fails. So how can we prevent this from happening?
Well, with support from people like you, we’re the first group in the world to design peptide
therapy that targets this channel. This peptide therapy restores the communication between
the channel and mitochondria and normalises energy production. This prevents the heart
from working too hard, reduces the stress on the heart and prevents it from getting
too big and failing. Currently with our clinical collaborators in Sydney we are on track to
translating this therapy to the clinical setting to decrease the devastating impact of this
silent killer.

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