Transcriber: Alhassan Hamoud Reviewer: Nika Kotnik
Thanks, everyone.
Back in the 1930s, there was a baseball player named Lou Gehrig,
a legendary player who played for the New York Yankees.
People called him the Iron Horse.
He played 2130 consecutive games,
a record that stood for 56 years.
During the 1938 season, Gehrig started to feel unwell.
He needed to squeeze the bats harder and was stumbling out in the field.
He pulled himself out and went to the clinic
where he was diagnosed with a type of motor neurone disease.
This disease forced him to retire at age 36 and took his life two years later.
The greatest baseball player of all time,
a healthy athletic adult at the prime of his career,
rendered wheelchair bound and respiratory dependent in a matter of months.
This disease is named Lou Gehrig Disease,
Motor Neuron Disease or amyotrophic lateral sclerosis - ALS.
What is a motor neurone disease?
It affects the nerves that are connected to the muscles,
giving them commands and allowing us to move, speak, eat and breathe.
Five thousand people are living with Motor Neurone Disease
in the UK at any one time.
There is one in 400 of us who will get ALS.
Globally, cases are set to substantially increase,
attributed mainly to an aging population.
Wouldn’t it be great to have treatment for ALS?
To this day Riluzole is the widely used drug for ALS treatment,
but it only prolongs the patient’s life by a few months.
It got FDA approval in 1995, and up until then,
neurons were thought to be the main cells affected by the disease.
But studying the disease in mice helped us to understand that there are
neighboring cells that contribute to the disease.
These neighbouring cells are called astrocytes.
They are star shaped cells
that constitute a third of all cell types in the human brain.
The reason why they were previously neglected
is because they were thought to merely be the glue of the nervous system.
However, in recent times,
astrocytes are gaining more attention in the scientific community
due to their critical role in the central nervous system.
For instance,
for neurons to fire the commands to the muscles they are connected to,
they need support from astrocytes in the form of nutrients,
maintaining their microenvironment and orchestrating their communication.
The lack of astrocyte support is one of the key factors
in the progression of various neurological diseases,
and it can even contribute to the death of neurons by releasing toxic substance
and causing inflammation.
Animal models definitely help to deepen our understanding about the disease,
but unfortunately it has not led to the much needed new treatments
for the human disease.
One of the most distinguishing features of the adult human brain
is the complexity and diversity of its astrocytes.
Astrocytes are three times bigger
and have 10 fold more processes than those of mouse astrocytes,
which might explain why we need to study this disease in human cells.
But how might this be possible?
In 2006, a Japanese stem cell researcher,
Shinya Yamanaka published a groundbreaking research,
showing that adult cells can be transformed back
into much earlier versions of themselves.
The so-called induced pluripotent stem cells
can become any cell in the human body.
In 2012, Shinya Yamanaka won the Nobel Prize in Physiology and Medicine
and since Yamanaka’s discovery,
we have been able to take skin cells from patients
and reprogrammed them back into stem cells.
Change the chemicals in the liquids that we use to guide them to become
the cell of interest.
I’m the final year Ph.D. student
at the Francis Crick Institute and University College London.
In the lab, we model ALS.
We use stem cells from patients and healthy donors
to make neurons and astrocytes.
We found that astrocytes are affected early on in the disease,
and display changes to alter its normal functions.
We can grow astrocytes together with neurons and study
the communication between these cells.
We found that astrocytes from patients fail to promote
the survival of neurons similar compared to their healthy counterparts.
We believe this results from loss of their supportive function in ALS.
In addition to gaining some sort of toxicity
that makes them harmful to neighbouring neurons.
The human stem cell approach that I have described
has allowed for efficient testing for hundreds of compounds
to find suitable drugs for ultimate patient benefit.
Studying human stem cells derived astrocytes and neurons
has provided us with unprecedented opportunity to understand more about
how the disease starts and develops,
and therefore identify new targets for potential treatments.
I've been studying astrocytes during the four years of my Ph.D. ,
and I’m amazed by their critical role in supporting neurons,
and it reminds me that we need to keep on supporting patients
and we need to keep on trying to find a cure for motor neurone disease,
so patients wouldn’t have to endure what Lou Gehrig
and countless others went through.
Last Sunday, I woke up to great news that filled me with hope.
United to end Motor Neurone Disease campaign has successfully secured
a government investment of 50 million pounds
thanks to the efforts from patients like
the former rugby player Doddie Weir and the support from carers, scientists,
clinicians and researchers and Motor Neurone Disease Association.
I'm hoping in the next few years we'll be able to cure Motor Neurone disease
and may be harnessing the potentials
of the neglected stars in supporting neurons would take us closer to our goal.
Thank you.