Please see below the latest Research Roundup letters from Parkinson’s UK

Research Roundup
Thank you for your continued support of Parkinson’s research, and a warm welcome if you are
new to the Research Support Network.
Study reveals benefits of physical activity for Parkinson’s symptoms
Researchers compared results from over 150 studies to understand how different types of
physical activity can be used to manage Parkinson’s symptoms.
Being physically active can have a positive impact on Parkinson’s symptoms, both physically
and mentally. Research has shown that aiming for 2.5 hours of physical activity a week can
help people with Parkinson’s take control of their condition. Read more about the benefits of
physical activity on our website.
While there are many different types of physical activity, some will naturally suit some people
better than others. However, it’s unknown whether some specific activities might be useful to
target particular symptoms. Or whether exercises should be advised at different stages of the
progression of the condition.
What did the researchers do?
The research team conducted a form of study called a Cochrane review. They analysed results
from 156 different studies involving different types of physical activity including dance,
aqua-based training and weight training. They looked at feedback from participants in these
studies to assess for changes in quality of life, and other common tests to monitor progression
of the condition.
Overall, the researchers found that taking part in physical activity had benefits for people with
Parkinson’s in terms of movement or improved quality of life, when compared with people who
had not been active.
It was not clear whether specific forms of physical activity were better than others for people
with Parkinson’s. The team did find some evidence that linked taking part in dance classes with
an improvement in balance and other symptoms associated with movement. They also found
that aqua-based training was linked to improvements in quality of life, although whether this
was due to physical activity or social interaction at exercise classes was unclear.
What does this mean?
This study, combining results collected from over 7,000 people with Parkinson’s, offers great
evidence that taking part in most types of physical activity can be beneficial for people with
Parkinson’s.
Importantly, there was very little evidence that physical activity resulted in harm, or worsening
of symptoms, for any participants.
Dr Becky Jones, Research Communications Officer at Parkinson’s UK, said:
“Reviews like this are a great example of how looking across results from many different
studies can provide us with a clearer picture of whether a treatment or an activity could be
beneficial for people with Parkinson’s. The study adds to our existing knowledge that physical
activity can be an important way for people with Parkinson’s to take control of the condition.
“The Cochrane review highlights exciting areas that need further study. More research into the
particular benefits of dance or aqua-based training could help guide people with Parkinson’s to
try out activities that could have the most impact on symptoms.
“As always, we recommend that anyone wishing to make a change to their lifestyle speak with
their healthcare provider for advice before starting.”
Early results offer new hope for dyskinesia treatment
We’re excited to announce the positive results of a trial for a potential new treatment for
people with Parkinson’s with levodopa-induced dyskinesia.
This is the first completed clinical trial funded by the Parkinson’s Virtual Biotech.
Dyskinesia is a debilitating side effect of current Parkinson’s medication, with around half (40
to 50%) of all people with Parkinson’s experiencing it after 5 years of taking levodopa, the
main drug used to treat the condition. Up to 80% experience it after 10 years.
With dyskinesia everyday tasks, such as eating, writing and walking, can become extremely
difficult. In fact, uncontrolled movement was voted the third most important issue to be
addressed by research in a recent Parkinson’s UK survey on quality of life. The main medication
available to manage dyskinesia is amantadine, which can have side effects and does not work
for everyone.
The study tested whether a drug called NLX-112 is safe to use in people with Parkinson’s. It
also looked at how effective it may be at reducing dyskinesia in people who take levodopa to
manage their Parkinson’s. Its safety has previously been confirmed in people with other
conditions.
Serotonin cells in the brain have the ability to convert levodopa into dopamine. These cells are
thought to contribute to the development of dyskinesia when they start to release dopamine
erratically. NLX-112 works by targeting serotonin cells inside the brain, and decreasing the
amount of dopamine the cells release.
Supported by the Parkinson’s Virtual Biotech
The clinical trial was co-funded by The Parkinson’s Virtual Biotech, the drug discovery arm of
Parkinson’s UK, and The Michael J Fox Foundation for Parkinson’s Research. The projects the
Parkinson’s Virtual Biotech funds are entirely driven by the Parkinson’s community and their
priorities.
This is the first completed clinical trial funded by the Parkinson’s Virtual Biotech, a global
partnership with the Parkinson’s Foundation. The promising results show that this innovative
way of working to fast-track the most promising breakthroughs through the drug development
pipeline is bringing us closer to new treatments.
What did the research set out to do?
The phase 2a clinical trial investigated how safe and well tolerated the drug was on a small
number of people with Parkinson’s. The trial also took a first look at the drug’s efficacy, which
is how well it does its job.
What did the clinical trial involve?
22 participants with Parkinson’s with levodopa-induced dyskinesia completed the 8-week trial
in Sweden. 15 participants received NLX-112 and 7 participants received a dummy drug.
Participants either received NLX-112 or the dummy drug in increasing doses during the initial
4 weeks, to minimise the potential side effects. They stayed on the maximum dose for 2 weeks,
and then were weaned off the drug over 2 weeks.
What were the results?
The results achieved the first objective to suggest that NLX-112 was safe and well tolerated in
people with Parkinson’s.
The second aim of the study was to show that NLX-112 was effective in treating dyskinesia.
The results suggest participants who received NLX-112 showed a significant reduction in their
scores for dyskinesia, whereas those who received the dummy drug did not show a significant
reduction in their scores.
The side effects of participants who received NLX-112 were mild, which confirmed previous
results.
What’s next?
Now that the phase 2a clinical trial has been completed, the researchers will complete a full
analysis of the results. They will then progress to a phase 2b clinical trial where they will
investigate the safety and efficacy of the drug in a larger group.
Dr Arthur Roach, Director of Research at Parkinson’s UK, said:
“We’re incredibly proud and excited by these early results from Neurolixis. They were one of
the first companies that the Parkinson’s Virtual Biotech invested in, in partnership with The
Michael J Fox Foundation, so to see it making positive progress just reiterates why this brave
and innovative approach is right for the Parkinson’s community. It really is bringing us closer to
new treatments that address the symptoms that the Parkinson’s community have told us are
the most urgent and levodopa-induced dyskinesias is one of those.
“Further studies will be necessary for regulatory approval and routine clinical use of NLX-112.
But now people with Parkinson’s can have hope that a much-needed new treatment for
levodopa-induced dyskinesias may be coming to them soon, and know that their support of the
Parkinson’s Virtual Biotech has made this possible.”
Best wishes,
Becky Jones
Research Communications Officer

Research Roundup
Thank you for your continued support of Parkinson’s research, and a warm welcome
if you are new to the Research Support Network.
Brain Awareness Week — studying the power of the brain’s
self-cleaning system
In March we marked Brain Awareness Week, a celebration of research being
undertaken to understand how the brain works, and crucially ways to help when
things go wrong.
At Parkinson’s UK, almost all of the research we fund relates to the brain in some
way. We know the symptoms of Parkinson’s are caused by a loss of a brain
chemical called dopamine. This is linked to the death of brain cells which produce it.
So whether the research is studying the brain more closely to look at what causes
this, studying the impact of certain drugs for treating symptoms. Or even studying
the effects of certain activities such as physical activity on mental health, it would
be tricky to study Parkinson’s without considering the brain along the way.
Some of the projects we fund look a bit more closely at how the condition develops
in the brain. One such project is being led by Dr Ian Harrison and Professor Mark
Lythgoe at University College London.
Ian and Mark are interested in how our brains normally get rid of waste products
which build up throughout the day. Failed clearance of these waste products can
lead to them building up in the brain, which can stop the cells from being able to
carry out their job as usual.
Many different neurodegenerative conditions are associated with a build up of brain
waste, normally in the form of clumps of sticky protein. In Parkinson’s, the
troublesome protein is called alpha-synuclein. Strands of the protein start to tangle
together and clog up brain cells, causing damage which ultimately results in cell
death.
Flushing away the waste
In our brains, we need a way to clear away the waste protein which builds up
throughout the day. Luckily, we have a built-in self-cleaning system, called the
glymphatic system, which kicks in while we sleep.
The glymphatic system is a network of fluid-filled spaces and water channels that
can carry this accumulated waste out of the brain. It uses cerebrospinal fluid, a clear
liquid which surrounds the brain, to wash away the toxic proteins and dead cells
that have built up during the day.
But in Parkinson’s and other neurodegenerative conditions such as Alzheimer’s, the
system is not able to clear away the toxic clumps of alpha-synuclein effectively. So
in 2019, alongside Alzheimer’s UK, we co-funded a project led by Ian to try and
understand whether there are ways to boost this system.
The project involves studying mice that have been injected with alpha-synuclein.
This injection triggers the alpha-synuclein already in the brain to start clumping
together, which then starts to accumulate in the brain. As alpha-synuclein clumps
form, they cause damage, and the clumps start to spread around other cells. This
means that the mice start to develop some of the symptoms associated with
Parkinson’s, such as movement problems.
To understand how the glymphatic system might be involved in the development of
Parkinson’s symptoms, Ian has been using a drug which stops the system working.
The drug targets a protein called aquaporin-4, which previous research has shown
is important in making sure the glymphatic system works correctly.
Ian’s results so far show that when the mice are given this drug, they experience
more problems with movement, and develop more clumps of alpha-synuclein in
areas of the brain. This suggests that the glymphatic system is important in
Parkinson’s — when it’s not working at all, the symptoms appear worse.
So is there a way to boost the glymphatic system?
Using the same mice, Ian is looking to address this question. This time, he’s using a
different drug, which can speed up the glymphatic system. It does this by increasing
the function of aquaporin-4. If it works, then he should see that the mice given this
drug have fewer issues with movement and fewer clumps of alpha-synuclein in
their brain cells. This work is still ongoing, but Ian is excited to see where this will
lead.
From mice to humans and back again
While using mice in research can be a really helpful tool to study what’s going on in
the brain during Parkinson’s, it doesn’t quite tell us the whole story of what’s
happening in humans. We need studies of human brains to understand the whole
picture.
Which is why Ian is working with Mark Lythgoe, Professor of Biomedical Imaging at
University College London, to find out more about what’s happening in the brains of
people with Parkinson’s.
Using tissue provided by the Parkinson’s UK Brain Bank, Ian and Mark are
comparing areas of the brain in people who had early and late stage Parkinson’s,
alongside people who didn’t have Parkinson’s.
They are looking for aquaporin-4, and for any clues that it might be linked to
increases in alpha-synuclein build up. When it’s working properly, aquaporin-4
should be found concentrated in one area of a particular type of brain cell. This
helps it perform its main function — moving cerebrospinal fluid into the brain, so
that the fluid can power the glymphatic system and clear away waste proteins. But
when it’s not working properly, aquaporin-4 can be found spread throughout the
cell, rather than concentrated to the one area.
Looking at the brain tissue has helped Ian and Mark piece together more of the
story that began by looking at the mice. In brain samples from people with late
stages of Parkinson’s, there is less aquaporin-4 when compared to samples from
people without Parkinson’s. And the aquaporin-4 that is there, isn’t where it should
be. All this suggests the glymphatic system might not be working properly.
However in people with early stages of Parkinson’s, there seems to be more
aquaporin-4 than in people without Parkinson’s. This seems counterintuitive, but it
could just mean that the body is trying harder to clear away the clumps of
alpha-synuclein that have already started to form. By increasing aquaporin-4, the
brain is trying to encourage the glymphatic system to work overtime, but
unfortunately this is not enough to clear away all the clumps of protein.
What’s the next stage?
Working with the Brain Bank tissue has helped Ian and Mark confirm some of what
they are seeing in their experiments with mice. Studying brain tissue donated by
people who have lived with Parkinson’s is invaluable to furthering our
understanding of Parkinson’s. And finding potential new treatments.
As well as looking for aquaporin-4, Ian and Mark have also been able to take
samples of alpha-synuclein from the Brain Bank tissue. This means that they have
real protein from people with Parkinson’s, which can be used for further studies.
One of the ways they hope to use this is to further their work in mice. Using this
alpha-synuclein, donated from people who had Parkinson’s, might help make the
study more representative of what’s going on in humans, instead of relying on an
artificial form of alpha-synuclein. They also hope to use these mice to work out the
best time to give a treatment which would boost the glymphatic system, making it
the most useful for people with Parkinson’s.
The work so far has shed light on how the glymphatic system might be involved in
Parkinson’s, and ways that we might be able to harness its power to pave the way
for new treatments to slow, or even stop, the progression of Parkinson’s.
Study reveals benefits of physical activity for Parkinson’s
symptoms
Researchers compared results from over 150 studies to understand how different
types of physical activity can be used to manage Parkinson’s symptoms.
Being physically active can have a positive impact on Parkinson’s symptoms, both
physically and mentally. Research has shown that aiming for 2.5 hours of physical
activity a week can help people with Parkinson’s take control of their condition.
Read more about the benefits of physical activity on our website.
While there are many different types of physical activity, some will naturally suit
some people better than others. However, it’s unknown whether some specific
activities might be useful to target particular symptoms. Or whether exercises
should be advised at different stages of the progression of the condition.
What did the researchers do?
The research team conducted a form of study called a Cochrane review. They
analysed results from 156 different studies involving different types of physical
activity including dance, aqua-based training and weight training. They looked at
feedback from participants in these studies to assess for changes in quality of life,
and other common tests to monitor progression of the condition.
Overall, the researchers found that taking part in physical activity had benefits for
people with Parkinson’s in terms of movement or improved quality of life, when
compared with people who had not been active.
It was not clear whether specific forms of physical activity were better than others
for people with Parkinson’s. The team did find some evidence that linked taking part
in dance classes with an improvement in balance and other symptoms associated
with movement. They also found that aqua-based training was linked to
improvements in quality of life, although whether this was due to physical activity
or social interaction at exercise classes was unclear.
What does this mean?
This study, combining results collected from over 7,000 people with Parkinson’s,
offers great evidence that taking part in most types of physical activity can be
beneficial for people with Parkinson’s.
Importantly, there was very little evidence that physical activity resulted in harm, or
worsening of symptoms, for any participants.
Dr Becky Jones, Research Communications Officer at Parkinson’s UK, said:
“Reviews like this are a great example of how looking across results from many
different studies can provide us with a clearer picture of whether a treatment or an
activity could be beneficial for people with Parkinson’s. The study adds to our
existing knowledge that physical activity can be an important way for people with
Parkinson’s to take control of the condition.
“The Cochrane review highlights exciting areas that need further study. More
research into the particular benefits of dance or aqua-based training could help
guide people with Parkinson’s to try out activities that could have the most impact
on symptoms.
“As always, we recommend that anyone wishing to make a change to their lifestyle
speak with their healthcare provider for advice before starting.”
Early results offer new hope for dyskinesia treatment
We’re excited to announce the positive results of a trial for a potential new
treatment for people with Parkinson’s with levodopa-induced dyskinesia.
This is the first completed clinical trial funded by the Parkinson’s Virtual Biotech.
Dyskinesia is a debilitating side effect of current Parkinson’s medication, with
around half (40 to 50%) of all people with Parkinson’s experiencing it after 5 years
of taking levodopa, the main drug used to treat the condition. Up to 80% experience
it after 10 years.
With dyskinesia everyday tasks, such as eating, writing and walking, can become
extremely difficult. In fact, uncontrolled movement was voted the third most
important issue to be addressed by research in a recent Parkinson’s UK survey on
quality of life. The main medication available to manage dyskinesia is amantadine,
which can have side effects and does not work for everyone.
The study tested whether a drug called NLX-112 is safe to use in people with
Parkinson’s. It also looked at how effective it may be at reducing dyskinesia in
people who take levodopa to manage their Parkinson’s. Its safety has previously
been confirmed in people with other conditions.
Serotonin cells in the brain have the ability to convert levodopa into dopamine.
These cells are thought to contribute to the development of dyskinesia when they
start to release dopamine erratically. NLX-112 works by targeting serotonin cells
inside the brain, and decreasing the amount of dopamine the cells release.
Supported by the Parkinson’s Virtual Biotech
The clinical trial was co-funded by The Parkinson’s Virtual Biotech, the drug
discovery arm of Parkinson’s UK, and The Michael J Fox Foundation for Parkinson’s
Research. The projects the Parkinson’s Virtual Biotech funds are entirely driven by
the Parkinson’s community and their priorities.
This is the first completed clinical trial funded by the Parkinson’s Virtual Biotech, a
global partnership with the Parkinson’s Foundation. The promising results show
that this innovative way of working to fast-track the most promising breakthroughs
through the drug development pipeline is bringing us closer to new treatments.
What did the research set out to do?
The phase 2a clinical trial investigated how safe and well tolerated the drug was on
a small number of people with Parkinson’s. The trial also took a first look at the
drug’s efficacy, which is how well it does its job.
What did the clinical trial involve?
22 participants with Parkinson’s with levodopa-induced dyskinesia completed the
8-week trial in Sweden. 15 participants received NLX-112 and 7 participants
received a dummy drug.
Participants either received NLX-112 or the dummy drug in increasing doses during
the initial 4 weeks, to minimise the potential side effects. They stayed on the
maximum dose for 2 weeks, and then were weaned off the drug over 2 weeks.
What were the results?
The results achieved the first objective to suggest that NLX-112 was safe and well
tolerated in people with Parkinson’s.
The second aim of the study was to show that NLX-112 was effective in treating
dyskinesia. The results suggest participants who received NLX-112 showed a
significant reduction in their scores for dyskinesia, whereas those who received the
dummy drug did not show a significant reduction in their scores.
The side effects of participants who received NLX-112 were mild, which confirmed
previous results.
What’s next?
Now that the phase 2a clinical trial has been completed, the researchers will
complete a full analysis of the results. They will then progress to a phase 2b clinical
trial where they will investigate the safety and efficacy of the drug in a larger group.
Dr Arthur Roach, Director of Research at Parkinson’s UK, said:
“We’re incredibly proud and excited by these early results from Neurolixis. They
were one of the first companies that the Parkinson’s Virtual Biotech invested in, in
partnership with The Michael J Fox Foundation, so to see it making positive
progress just reiterates why this brave and innovative approach is right for the
Parkinson’s community. It really is bringing us closer to new treatments that
address the symptoms that the Parkinson’s community have told us are the most
urgent and levodopa-induced dyskinesias is one of those.
“Further studies will be necessary for regulatory approval and routine clinical use of
NLX-112. But now people with Parkinson’s can have hope that a much-needed new
treatment for levodopa-induced dyskinesias may be coming to them soon, and
know that their support of the Parkinson’s Virtual Biotech has made this possible.”
Best wishes,
Becky Jones
Research Communications Officer