November 3, 2024 • 21 mins
In Australia alone, 50 people are diagnosed with Parkinson's every day. Therapy options are limited, as they are for other movement and muscle disorders, such as ataxia and dystonia. In this episode of Medical Minds, we meet neurologist and researcher Associate Professor Kishore Kumar, who is working on the next big breakthroughs for treatment.
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Dr Viviane Richter (00:01):
Muhammad Ali, Michael J. Fox, Billy Connolly. A few of
many well-known people who all share one thing in common.
They were all diagnosed with Parkinson's disease. In Australia, 50
people are diagnosed every day and therapy options for Parkinson's,
as well as for other movement and muscle disorders such
(00:22):
as ataxia and dystonia, are limited. So, what could be
the next big breakthrough in treatment? Welcome to Medical Minds,
the podcast that takes you inside the labs at the
Garvan Institute of Medical Research. I'm your host, Dr Vivian Richter.
And with me here is Associate Professor Kishore Kumar, leader
of the Translational Neuro Genomics Group at Garvan. Welcome, Kishore.
Associate Professor Kishore Kumar (00:46):
Thanks, Viv. Great to be here.
Dr Viviane Richter (00:48):
Kishore, you're a neurologist who sees patients with movement disorders
on a regular basis. Can you give us a bit
of an insight into your clinic?
Associate Professor Kishore Kumar (00:57):
I'm referred patients from a general practitioner or another neurologist.
They often have a movement disorder, so they may have
some trouble walking, some trouble with fine movements, speed of
movements or stiffness. The doctor might recognise they have Parkinson's
disease and they'll refer them, the case, to me. Or
they may refer a case when they suspect that the
(01:18):
patient has cerebellar ataxia, which is a disorder of co-ordination
and balance. I also see patients with hereditary spastic paraplegia.
This is a condition of weakness and stiffness in the
legs that progresses over time. And finally, I also see
patients with dystonia, which is a involuntary muscle contraction and
(01:39):
twisting movement. The process when I see a patient, I
go through a detailed history where I talk to the patient,
find out their symptoms and then do an examination and
then decide what investigations, further tests or treatments are required.
Dr Viviane Richter (01:56):
Kishore, how prevalent are these conditions and what does the
the treatment pathway look like?
Associate Professor Kishore Kumar (02:02):
The prevalence of Parkinson's is actually quite common. It's anywhere
between 1 to 3% of people over the age of 65.
So there are over 150,000 people with Parkinson's in Australia,
and about 10% of those are familial. That's early-onset or
people with a positive family history of Parkinson's disease. Then
(02:25):
for dystonia, that's, um, more rarer, so that's about 16
per 100,000 people. And for those other two conditions I mentioned,
which is ataxia or hereditary spastic paraplegia, about 10 per
100,000 people. So these are rare disorders.
Dr Viviane Richter (02:41):
And what would treatment typically look like?
Associate Professor Kishore Kumar (02:44):
So, we've known about Parkinson's for a long time, and
it was first, it was named by James Parkinson in
an essay in 1817. And over the last few years
and many decades, the basic treatment of Parkinson's hasn't changed. Essentially,
you're replacing dopamine with medications, levodopa medications, or you're using
(03:06):
a different type of treatment called a dopamine agonist. So,
this is a drug that binds the dopamine receptor. So,
it's all about replacing the dopamine or compensating for the
lack of dopamine. And, more recently, we've had different treatments,
like deep brain stimulation, which is an operation where they
insert electrodes into the brain and stimulate the brain. And
(03:26):
this is an effective treatment. But again, this treatment has
been around for a long time. The treatments for dystonia
are also very limited. They include injections into the muscle
with botulinum toxin injections to overcome the excessive muscle contraction. The
treatment for ataxia is very limited. It's really physiotherapy and
(03:48):
occupational therapy supportive treatments. Uh, and it's the same for
hereditary spastic paraplegia, but you can use injections into the muscle,
botulinum toxin injections.
Dr Viviane Richter (03:59):
Do we know what causes these conditions?
Associate Professor Kishore Kumar (04:01):
We don't know enough about what causes these conditions, and
that's part of looking at the genes to find out
more about what the genes do and what the proteins do.
But for Parkinson's disease, we know that there's part of
the brain stem called the substantia nigra. There's cells that
produce dopamine, and there's lots of these dopamine producing cells.
(04:22):
And if you look at the pathology, there's a characteristic
finding called Lewy bodies. And if you look inside the
Lewy bodies, you see alpha-synuclein. And it's thought that this protein, alpha-synuclein,
is key to Parkinson's disease. And a lot of the
new treatments are built around trying to address this perceived
(04:42):
build up of alpha-synuclein.
Dr Viviane Richter (04:45):
Tell us how you came to be working in this
space and how our genes are linked to these conditions.
Associate Professor Kishore Kumar (04:51):
I, uh, started, uh, neurology training because there's something about
neurology that's really amazing. Uh, neurology is all about taking
a history, listening to people tell their story and then
examining them very carefully, and a lot of it's to
do with observation and observing things. And then it's quite
(05:11):
intellectual where you're really thinking about the history examination and
coming up with a diagnosis, and there often isn't a
very easy answer. And, until recently, we didn't have really
obvious tests to tell a person what the reason they
have a particular disorder. And I think that's the really
nice thing about genetic testing, because you can often say,
(05:32):
in a black or white way, that a person has
a disorder due to a single change in their DNA,
and you can point to that and explain to them
what their problem is. So, you can take out this
mystery and solve the mystery with a genetic test. That's
very nice for patients. I think they really like to
have an answer.
Dr Viviane Richter (05:53):
So how does a genetic diagnosis help?
Associate Professor Kishore Kumar (05:55):
Apart from just giving people an answer, which is valuable
in its own right, you can give the patient proper
genetic counselling. You can give them advice on how the
condition can affect other family members. And sometimes you can
restore their confidence about starting a family, what we call
reproductive confidence. And, in some cases, you can prevent a
(06:19):
gene mutation from being passed on to someone's children, which
is very powerful, and that's through selecting embryos that don't
carry the mutation and having IVF. And this is a
very powerful way to prevent a disease from being transmitted
down the family. And then, in itself, we can tell
people a bit about what they could expect about the
(06:40):
disease course. So, for Parkinson's disease, we have a gene
called PRKN and PINK1, and what we know about PRKN
and PINK1 is that people with this gene tend to
have a very benign course. They tend to progress very slowly.
They don't get memory problems and cognitive problems in dementia,
(07:02):
and they respond very well to drug treatments like levodopa
treatments and deep brain stimulation. Whereas, if you have other genes,
sometimes they don't respond so well. There's a gene called
GBA or glucocerebrosidase. If you have this gene, if we
look at a big group of people, people with the
GBA gene and Parkinson's tend to progress more rapidly. They
(07:25):
have a more rapid progression. They tend to get more
memory problems, and they tend to do not so well
after deep brain stimulation. This area is under a lot
of research to really understand it a bit more about
how it changes over time, how the disease course changes. Now,
we have some treatments, in some cases, a genetic diagnosis
(07:47):
can actually change your treatment. The other day we diagnosed
a patient with ataxia, the disorder of balance, with a newly
described genetic form of ataxia. It's called FGF14. It's a
stutter in the FGF14 gene, which we helped discover, and
we diagnosed this patient and started a new treatment, a
(08:09):
treatment called Fampyra, and the patient had a a really
dramatic response, and they improved and they had less episodes
of ataxia. This is a great example of how a
genetic diagnosis can change a person's treatment. And in the future,
we hope that a genetic finding can be linked with
a precision treatment that addresses the underlying genetic cause. And
(08:33):
this is something that will occur if we do clinical
trials and base it on the underlying gene abnormality.
Dr Viviane Richter (08:40):
Who is most likely to develop Parkinson's disease?
Associate Professor Kishore Kumar (08:43):
That's a great question. So, Parkinson's is more common as
you get older, and it's affecting people over the age
of 65 in particular. But a certain proportion of patients
are young-onset Parkinson's, and we've defined that as being having Parkinson's
with the age of onset below the age of 50. So,
(09:04):
this young-onset Parkinson's is about 10% of cases and people with
young onset Parkinson's have to deal with quite a lot.
They have to deal with the fact that they're usually working.
They might be parents to young children, and these have
specific and special challenges to having Parkinson's at a young age.
And this is certainly one of my areas of interest.
(09:26):
And my focus is to try to understand why people
get Parkinson's at a young age and how better to
assist them and help them.
Dr Viviane Richter (09:34):
So, tell us about your research in this area.
Associate Professor Kishore Kumar (09:37):
We've got a really exciting project for Parkinson's disease. It's
called the Monogenic Parkinson's Disease Australia Study, or MonoPDAus. We're linking with
an existing study called the Australian Parkinson's Genetic Study. This
study recruits people from around Australia, 10,000 people who are
prescribed Parkinson's disease medication. We're going to prioritise patients who
(10:02):
have young-onset Parkinson's and those with a positive family history. These
are people we expect to have a genetic cause, and
we're going to do whole genome sequencing, which is a
test where we screen your entire genetic code in a
single test. We're going to interpret the results and return
(10:23):
the results back to the patients, and then try and
understand the benefits of genetic testing through surveys and health
economic studies. And this way we can prove that there's
a benefit to genetic testing in Parkinson's, because right now
people don't get genetic testing in a uniform or fair way.
There's no genetic testing Medicare rebate for Parkinson's, and we
(10:46):
want to prove that there's a benefit so that we
can move forward with broad genetic testing for Parkinson's disease.
Dr Viviane Richter (10:53):
And I guess it's about giving people that certainty, right?
Associate Professor Kishore Kumar (10:55):
Yeah, we want to give people an answer as to
why they have Parkinson's and give them clues as to
what they might expect. How might the disease progress over time?
How might the disease respond to different treatments like drugs
or deep brain stimulation? This is information that both the
patient and their doctors are going to find very valuable.
Dr Viviane Richter (11:18):
Is genetic testing currently used for other movement disorders?
Associate Professor Kishore Kumar (11:22):
Genetic testing is used for a range of different movement
disorders such as ataxia, dystonia and hereditary spastic paraplegia. So,
at the moment, ataxia is diagnosed through a series of
different tests. About ten different tests are used to diagnose ataxia.
And by the end of that process, many patients are
(11:44):
still undiagnosed. Uh, we've developed a new test, using long-read
sequencing with the Oxford Nanopore long-read sequencing, which allows us to
streamline that process. And in a single test, we're able
to pick up all the stutters in the DNA, the
repeat expansions and spelling errors in the DNA, a whole
(12:04):
range of different mutation types, and it's giving us a
very high diagnostic rate. That means if you have the test,
you're likely to get an answer in about 40% of cases. So,
this is a vast improvement on what we were doing previously,
and we think it will replace the existing technology we
have at the moment.
Dr Viviane Richter (12:23):
What does this mean for patients?
Associate Professor Kishore Kumar (12:25):
This means that we can give you a genetic diagnosis,
where before you didn't have one, and a great example
is a cause of late-onset ataxia. Ataxia is occurring late
in life. We helped discover this, it's called an expansion
in a gene called FGF14. So, a stutter in the
gene FGF14 and, using Nanopore sequencing, we're able to accurately
(12:49):
detect those cases with the stutter in the FGF14 gene.
It turns out this is a very common cause of
late-onset ataxia. Already there are over 800 cases found worldwide,
and the incredible thing is that this particular type of
ataxia is responsive to a drug. The drug is called fampridine,
(13:13):
and when patients take this drug, 80% of them will
get a really good response. They'll stop getting bouts of ataxia.
Certainly from my personal experience, and I've seen a patient
a few days ago who had a dramatic response to
this treatment, and it really made a huge impact on
his life. He said he's gone from being fairly miserable to
being really having a good quality of life from this drug.
Dr Viviane Richter (13:37):
Kishore, you also specialise in dystonia. Can you tell us
a little bit more about this and whether there are
any breakthrough treatments on the horizon?
Associate Professor Kishore Kumar (13:47):
Dystonia is an involuntary muscle contraction, which can also be
often be very uncomfortable for people who suffer from this disorder. So,
it can involve part of the body, like the the
head or the neck, turning of the head or the neck.
It can involve your hands, and it can cause things
like writer's cramp or, in golfing, the yips. It can be a
(14:10):
form of dystonia. Some people could play a musical instrument
and get abnormal position of their hands, uh, musician's dystonia. So,
dystonia can affect different parts of the body, and it
can be very unpleasant for people who suffer this condition.
And one of the problems is the treatment hasn't changed much.
It's still injections into the muscle with botulinum toxin injections. And,
(14:34):
in some cases, such as severe generalised dystonia, your doctor
may consider a treatment such as deep brain stimulation, which
is surgical treatment with electrodes into the brain, and this
can be an effective treatment. What we currently don't have
is an ability to predict how people respond to deep
brain stimulation. Through our research, we set up the first
(14:56):
whole genome sequencing database for dystonia in the world in Australia,
and we use that database to show that certain genetic
forms of dystonia respond well to deep brain stimulation, and
some forms don't respond well. Another problem we're hoping to
tackle is the low diagnostic rate, with only 10% of
(15:16):
patients getting a diagnosis from the first initial study. But,
we've used various approaches and looking at the data in
different ways to boost the diagnostic rate up to 18%.
And now we're looking to apply highly advanced technology through
the Garvan Institute to boost that diagnostic rate even further,
up to 30 or 40%. So that's tripling or quadrupling
(15:38):
the diagnostic rate and giving more people an answer as
to why they have dystonia.
Dr Viviane Richter (15:44):
And the ultimate goal of this research is to be
integrated into routine clinical practice, as you've mentioned. With this
genetic testing implemented, what does a future visit to a neurologist,
to someone like you, look like?
Associate Professor Kishore Kumar (16:00):
Viv, at the moment, when someone sees a neurologist, they
get a history, they get an examination. They get some tests,
often an MRI, and then the neurologist decides on their
treatment from the clinical picture. Patients usually get the same
treatment based on the condition that they have. But in
the future, I hope one of the tests that the
(16:20):
neurologist orders is a genetic test, that everyone has a
chance to have a genetic test, that that result will
come back, and that will help inform the way that
the neurologist treats the patient. And that patients will get
a precision medicine approach, a personalised treatment based on their
underlying gene abnormality that better targets their condition to improve
(16:44):
patient care.
Dr Viviane Richter (16:46):
Kishore, you see patients on a regular basis. What is
your hope for them?
Associate Professor Kishore Kumar (16:52):
It's hard to be a neurologist dealing with these conditions
because these conditions are neurodegenerative disorders often, and they often
get worse over time and they're not curable. But I
always see some hope in my patients and even giving
things like physiotherapy, occupational therapy, giving people proper care, staying
(17:14):
with your patients and seeing them regularly can give them hope.
And I think there's a lot to be hopeful about.
I think the field is changing very rapidly and new
treatments are coming on the horizon. They're already coming for
muscle diseases and they will follow Parkinson's disease as well
and dystonia. New treatments will come and we have a
lot to be hopeful about with the future. The medical
(17:36):
field is changing very rapidly. Genomics will drive that change.
The future will be brighter than it is now for sure.
Dr Viviane Richter (17:44):
Kishore, before we let you get back to the lab
or the clinic, it's time for the fast five.
Associate Professor Kishore Kumar (17:50):
OK.
Dr Viviane Richter (17:51):
You ready?
Associate Professor Kishore Kumar (17:52):
Yep, ready.
Dr Viviane Richter (17:53):
Do you have a favourite band?
Associate Professor Kishore Kumar (17:54):
Favourite band? My kids have have five singers they have
on repeat
forgotten the other two.
Dr Viviane Richter (18:05):
So, they're your favourite?
Associate Professor Kishore Kumar (18:06):
They're not my favourite bands. But this is all that
we listen to in the car. Yeah.
Dr Viviane Richter (18:11):
Do you have a favourite quote or life motto that
resonates with you?
Associate Professor Kishore Kumar (18:16):
Actually, I really think never giving up and persisting despite
all the challenges that you might face. Working really hard
and and being kind to people and polite to people
and respectful. And I think this is really important because
clinical work and research, it can be very stressful. And
I think we should all treat each other really politely
(18:36):
and respectfully and try to support each other through a
very challenging career.
Dr Viviane Richter (18:42):
What's your favourite way to get exercise?
Associate Professor Kishore Kumar (18:45):
So, I, I just go to the gym and run
on the treadmill. This is a bit boring. But in
the Parkinson's, uh, meeting in Philadelphia, and every year, we
have an international Parkinson's meeting and there's a five kilometre run.
And I'm determined to do well at that five kilometre run,
and run it alongside other neurologists and, uh, hopefully I'll
be able to finish in a reasonable place. So, that's
(19:08):
that's my goal. I'm working towards this run at the
Parkinson's meeting.
Dr Viviane Richter (19:12):
What's the current book you're reading?
Associate Professor Kishore Kumar (19:14):
Uh, the current book I'm reading is called Unruly by
David Mitchell, and it's a take on the on British history.
And we're really fans of David Mitchell from his comedy
work on the BBC and uh, all the great shows
that we watch. So, I'm looking forward to reading this book.
Dr Viviane Richter (19:30):
Who inspires you the most?
Associate Professor Kishore Kumar (19:32):
Well, I'm obviously, I'm inspired by my wife. And I'm
not just saying that, but she's just an amazing person.
She puts up with me quite a lot with this,
with working so much late hours. But she's an inspirational person,
and she is a dentist, and she also works with
the university and does her own research. And she's an
inspiration to me. My family, my daughters are also amazing
(19:55):
little humans who inspire me as well. At work, I'm inspired
by some amazing mentors. Professor Carolyn Sue, who was a
mentor for my research, and Professor Christine Klein, who's just
an amazing researcher in Germany who I did my PhD with.
And I work with such amazing scientists around the Garvan, like Ira Deveson.
(20:17):
I'm working with scientists in at Concord, uh, Marina Kennerson. So,
I've got so many amazing people to inspire me and
great mentors in my life. So, I'm very lucky.
Dr Viviane Richter (20:27):
Associate Professor Kishore Kumar, thank you so much for joining
us on Medical Minds.
Associate Professor Kishore Kumar (20:32):
Thank you so much, Viv.
Dr Viviane Richter (20:34):
If you'd like to know more about Kishore's research or
donate to the work we do at Garvan, head to garvan.org.au.
Garvan is leading the Australian Parkinson's Mission, which is currently
recruiting trial participants. This is one of several research programmes
at Garvan investigating Parkinson's disease. If you or someone you
know is interested in participating, please visit this website
(21:02):
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening. This podcast was recorded on the traditional Country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.
Muhammad Ali, Michael J. Fox, Billy Connolly. A few of
many well-known people who all share one thing in common.
They were all diagnosed with Parkinson's disease. In Australia, 50
people are diagnosed every day and therapy options for Parkinson's,
as well as for other movement and muscle disorders such
(00:22):
as ataxia and dystonia, are limited. So, what could be
the next big breakthrough in treatment? Welcome to Medical Minds,
the podcast that takes you inside the labs at the
Garvan Institute of Medical Research. I'm your host, Dr Vivian Richter.
And with me here is Associate Professor Kishore Kumar, leader
of the Translational Neuro Genomics Group at Garvan. Welcome, Kishore.
Associate Professor Kishore Kumar (00:46):
Thanks, Viv. Great to be here.
Dr Viviane Richter (00:48):
Kishore, you're a neurologist who sees patients with movement disorders
on a regular basis. Can you give us a bit
of an insight into your clinic?
Associate Professor Kishore Kumar (00:57):
I'm referred patients from a general practitioner or another neurologist.
They often have a movement disorder, so they may have
some trouble walking, some trouble with fine movements, speed of
movements or stiffness. The doctor might recognise they have Parkinson's
disease and they'll refer them, the case, to me. Or
they may refer a case when they suspect that the
(01:18):
patient has cerebellar ataxia, which is a disorder of co-ordination
and balance. I also see patients with hereditary spastic paraplegia.
This is a condition of weakness and stiffness in the
legs that progresses over time. And finally, I also see
patients with dystonia, which is a involuntary muscle contraction and
(01:39):
twisting movement. The process when I see a patient, I
go through a detailed history where I talk to the patient,
find out their symptoms and then do an examination and
then decide what investigations, further tests or treatments are required.
Dr Viviane Richter (01:56):
Kishore, how prevalent are these conditions and what does the
the treatment pathway look like?
Associate Professor Kishore Kumar (02:02):
The prevalence of Parkinson's is actually quite common. It's anywhere
between 1 to 3% of people over the age of 65.
So there are over 150,000 people with Parkinson's in Australia,
and about 10% of those are familial. That's early-onset or
people with a positive family history of Parkinson's disease. Then
(02:25):
for dystonia, that's, um, more rarer, so that's about 16
per 100,000 people. And for those other two conditions I mentioned,
which is ataxia or hereditary spastic paraplegia, about 10 per
100,000 people. So these are rare disorders.
Dr Viviane Richter (02:41):
And what would treatment typically look like?
Associate Professor Kishore Kumar (02:44):
So, we've known about Parkinson's for a long time, and
it was first, it was named by James Parkinson in
an essay in 1817. And over the last few years
and many decades, the basic treatment of Parkinson's hasn't changed. Essentially,
you're replacing dopamine with medications, levodopa medications, or you're using
(03:06):
a different type of treatment called a dopamine agonist. So,
this is a drug that binds the dopamine receptor. So,
it's all about replacing the dopamine or compensating for the
lack of dopamine. And, more recently, we've had different treatments,
like deep brain stimulation, which is an operation where they
insert electrodes into the brain and stimulate the brain. And
(03:26):
this is an effective treatment. But again, this treatment has
been around for a long time. The treatments for dystonia
are also very limited. They include injections into the muscle
with botulinum toxin injections to overcome the excessive muscle contraction. The
treatment for ataxia is very limited. It's really physiotherapy and
(03:48):
occupational therapy supportive treatments. Uh, and it's the same for
hereditary spastic paraplegia, but you can use injections into the muscle,
botulinum toxin injections.
Dr Viviane Richter (03:59):
Do we know what causes these conditions?
Associate Professor Kishore Kumar (04:01):
We don't know enough about what causes these conditions, and
that's part of looking at the genes to find out
more about what the genes do and what the proteins do.
But for Parkinson's disease, we know that there's part of
the brain stem called the substantia nigra. There's cells that
produce dopamine, and there's lots of these dopamine producing cells.
(04:22):
And if you look at the pathology, there's a characteristic
finding called Lewy bodies. And if you look inside the
Lewy bodies, you see alpha-synuclein. And it's thought that this protein, alpha-synuclein,
is key to Parkinson's disease. And a lot of the
new treatments are built around trying to address this perceived
(04:42):
build up of alpha-synuclein.
Dr Viviane Richter (04:45):
Tell us how you came to be working in this
space and how our genes are linked to these conditions.
Associate Professor Kishore Kumar (04:51):
I, uh, started, uh, neurology training because there's something about
neurology that's really amazing. Uh, neurology is all about taking
a history, listening to people tell their story and then
examining them very carefully, and a lot of it's to
do with observation and observing things. And then it's quite
(05:11):
intellectual where you're really thinking about the history examination and
coming up with a diagnosis, and there often isn't a
very easy answer. And, until recently, we didn't have really
obvious tests to tell a person what the reason they
have a particular disorder. And I think that's the really
nice thing about genetic testing, because you can often say,
(05:32):
in a black or white way, that a person has
a disorder due to a single change in their DNA,
and you can point to that and explain to them
what their problem is. So, you can take out this
mystery and solve the mystery with a genetic test. That's
very nice for patients. I think they really like to
have an answer.
Dr Viviane Richter (05:53):
So how does a genetic diagnosis help?
Associate Professor Kishore Kumar (05:55):
Apart from just giving people an answer, which is valuable
in its own right, you can give the patient proper
genetic counselling. You can give them advice on how the
condition can affect other family members. And sometimes you can
restore their confidence about starting a family, what we call
reproductive confidence. And, in some cases, you can prevent a
(06:19):
gene mutation from being passed on to someone's children, which
is very powerful, and that's through selecting embryos that don't
carry the mutation and having IVF. And this is a
very powerful way to prevent a disease from being transmitted
down the family. And then, in itself, we can tell
people a bit about what they could expect about the
(06:40):
disease course. So, for Parkinson's disease, we have a gene
called PRKN and PINK1, and what we know about PRKN
and PINK1 is that people with this gene tend to
have a very benign course. They tend to progress very slowly.
They don't get memory problems and cognitive problems in dementia,
(07:02):
and they respond very well to drug treatments like levodopa
treatments and deep brain stimulation. Whereas, if you have other genes,
sometimes they don't respond so well. There's a gene called
GBA or glucocerebrosidase. If you have this gene, if we
look at a big group of people, people with the
GBA gene and Parkinson's tend to progress more rapidly. They
(07:25):
have a more rapid progression. They tend to get more
memory problems, and they tend to do not so well
after deep brain stimulation. This area is under a lot
of research to really understand it a bit more about
how it changes over time, how the disease course changes. Now,
we have some treatments, in some cases, a genetic diagnosis
(07:47):
can actually change your treatment. The other day we diagnosed
a patient with ataxia, the disorder of balance, with a newly
described genetic form of ataxia. It's called FGF14. It's a
stutter in the FGF14 gene, which we helped discover, and
we diagnosed this patient and started a new treatment, a
(08:09):
treatment called Fampyra, and the patient had a a really
dramatic response, and they improved and they had less episodes
of ataxia. This is a great example of how a
genetic diagnosis can change a person's treatment. And in the future,
we hope that a genetic finding can be linked with
a precision treatment that addresses the underlying genetic cause. And
(08:33):
this is something that will occur if we do clinical
trials and base it on the underlying gene abnormality.
Dr Viviane Richter (08:40):
Who is most likely to develop Parkinson's disease?
Associate Professor Kishore Kumar (08:43):
That's a great question. So, Parkinson's is more common as
you get older, and it's affecting people over the age
of 65 in particular. But a certain proportion of patients
are young-onset Parkinson's, and we've defined that as being having Parkinson's
with the age of onset below the age of 50. So,
(09:04):
this young-onset Parkinson's is about 10% of cases and people with
young onset Parkinson's have to deal with quite a lot.
They have to deal with the fact that they're usually working.
They might be parents to young children, and these have
specific and special challenges to having Parkinson's at a young age.
And this is certainly one of my areas of interest.
(09:26):
And my focus is to try to understand why people
get Parkinson's at a young age and how better to
assist them and help them.
Dr Viviane Richter (09:34):
So, tell us about your research in this area.
Associate Professor Kishore Kumar (09:37):
We've got a really exciting project for Parkinson's disease. It's
called the Monogenic Parkinson's Disease Australia Study, or MonoPDAus. We're linking with
an existing study called the Australian Parkinson's Genetic Study. This
study recruits people from around Australia, 10,000 people who are
prescribed Parkinson's disease medication. We're going to prioritise patients who
(10:02):
have young-onset Parkinson's and those with a positive family history. These
are people we expect to have a genetic cause, and
we're going to do whole genome sequencing, which is a
test where we screen your entire genetic code in a
single test. We're going to interpret the results and return
(10:23):
the results back to the patients, and then try and
understand the benefits of genetic testing through surveys and health
economic studies. And this way we can prove that there's
a benefit to genetic testing in Parkinson's, because right now
people don't get genetic testing in a uniform or fair way.
There's no genetic testing Medicare rebate for Parkinson's, and we
(10:46):
want to prove that there's a benefit so that we
can move forward with broad genetic testing for Parkinson's disease.
Dr Viviane Richter (10:53):
And I guess it's about giving people that certainty, right?
Associate Professor Kishore Kumar (10:55):
Yeah, we want to give people an answer as to
why they have Parkinson's and give them clues as to
what they might expect. How might the disease progress over time?
How might the disease respond to different treatments like drugs
or deep brain stimulation? This is information that both the
patient and their doctors are going to find very valuable.
Dr Viviane Richter (11:18):
Is genetic testing currently used for other movement disorders?
Associate Professor Kishore Kumar (11:22):
Genetic testing is used for a range of different movement
disorders such as ataxia, dystonia and hereditary spastic paraplegia. So,
at the moment, ataxia is diagnosed through a series of
different tests. About ten different tests are used to diagnose ataxia.
And by the end of that process, many patients are
(11:44):
still undiagnosed. Uh, we've developed a new test, using long-read
sequencing with the Oxford Nanopore long-read sequencing, which allows us to
streamline that process. And in a single test, we're able
to pick up all the stutters in the DNA, the
repeat expansions and spelling errors in the DNA, a whole
(12:04):
range of different mutation types, and it's giving us a
very high diagnostic rate. That means if you have the test,
you're likely to get an answer in about 40% of cases. So,
this is a vast improvement on what we were doing previously,
and we think it will replace the existing technology we
have at the moment.
Dr Viviane Richter (12:23):
What does this mean for patients?
Associate Professor Kishore Kumar (12:25):
This means that we can give you a genetic diagnosis,
where before you didn't have one, and a great example
is a cause of late-onset ataxia. Ataxia is occurring late
in life. We helped discover this, it's called an expansion
in a gene called FGF14. So, a stutter in the
gene FGF14 and, using Nanopore sequencing, we're able to accurately
(12:49):
detect those cases with the stutter in the FGF14 gene.
It turns out this is a very common cause of
late-onset ataxia. Already there are over 800 cases found worldwide,
and the incredible thing is that this particular type of
ataxia is responsive to a drug. The drug is called fampridine,
(13:13):
and when patients take this drug, 80% of them will
get a really good response. They'll stop getting bouts of ataxia.
Certainly from my personal experience, and I've seen a patient
a few days ago who had a dramatic response to
this treatment, and it really made a huge impact on
his life. He said he's gone from being fairly miserable to
being really having a good quality of life from this drug.
Dr Viviane Richter (13:37):
Kishore, you also specialise in dystonia. Can you tell us
a little bit more about this and whether there are
any breakthrough treatments on the horizon?
Associate Professor Kishore Kumar (13:47):
Dystonia is an involuntary muscle contraction, which can also be
often be very uncomfortable for people who suffer from this disorder. So,
it can involve part of the body, like the the
head or the neck, turning of the head or the neck.
It can involve your hands, and it can cause things
like writer's cramp or, in golfing, the yips. It can be a
(14:10):
form of dystonia. Some people could play a musical instrument
and get abnormal position of their hands, uh, musician's dystonia. So,
dystonia can affect different parts of the body, and it
can be very unpleasant for people who suffer this condition.
And one of the problems is the treatment hasn't changed much.
It's still injections into the muscle with botulinum toxin injections. And,
(14:34):
in some cases, such as severe generalised dystonia, your doctor
may consider a treatment such as deep brain stimulation, which
is surgical treatment with electrodes into the brain, and this
can be an effective treatment. What we currently don't have
is an ability to predict how people respond to deep
brain stimulation. Through our research, we set up the first
(14:56):
whole genome sequencing database for dystonia in the world in Australia,
and we use that database to show that certain genetic
forms of dystonia respond well to deep brain stimulation, and
some forms don't respond well. Another problem we're hoping to
tackle is the low diagnostic rate, with only 10% of
(15:16):
patients getting a diagnosis from the first initial study. But,
we've used various approaches and looking at the data in
different ways to boost the diagnostic rate up to 18%.
And now we're looking to apply highly advanced technology through
the Garvan Institute to boost that diagnostic rate even further,
up to 30 or 40%. So that's tripling or quadrupling
(15:38):
the diagnostic rate and giving more people an answer as
to why they have dystonia.
Dr Viviane Richter (15:44):
And the ultimate goal of this research is to be
integrated into routine clinical practice, as you've mentioned. With this
genetic testing implemented, what does a future visit to a neurologist,
to someone like you, look like?
Associate Professor Kishore Kumar (16:00):
Viv, at the moment, when someone sees a neurologist, they
get a history, they get an examination. They get some tests,
often an MRI, and then the neurologist decides on their
treatment from the clinical picture. Patients usually get the same
treatment based on the condition that they have. But in
the future, I hope one of the tests that the
(16:20):
neurologist orders is a genetic test, that everyone has a
chance to have a genetic test, that that result will
come back, and that will help inform the way that
the neurologist treats the patient. And that patients will get
a precision medicine approach, a personalised treatment based on their
underlying gene abnormality that better targets their condition to improve
(16:44):
patient care.
Dr Viviane Richter (16:46):
Kishore, you see patients on a regular basis. What is
your hope for them?
Associate Professor Kishore Kumar (16:52):
It's hard to be a neurologist dealing with these conditions
because these conditions are neurodegenerative disorders often, and they often
get worse over time and they're not curable. But I
always see some hope in my patients and even giving
things like physiotherapy, occupational therapy, giving people proper care, staying
(17:14):
with your patients and seeing them regularly can give them hope.
And I think there's a lot to be hopeful about.
I think the field is changing very rapidly and new
treatments are coming on the horizon. They're already coming for
muscle diseases and they will follow Parkinson's disease as well
and dystonia. New treatments will come and we have a
lot to be hopeful about with the future. The medical
(17:36):
field is changing very rapidly. Genomics will drive that change.
The future will be brighter than it is now for sure.
Dr Viviane Richter (17:44):
Kishore, before we let you get back to the lab
or the clinic, it's time for the fast five.
Associate Professor Kishore Kumar (17:50):
OK.
Dr Viviane Richter (17:51):
You ready?
Associate Professor Kishore Kumar (17:52):
Yep, ready.
Dr Viviane Richter (17:53):
Do you have a favourite band?
Associate Professor Kishore Kumar (17:54):
Favourite band? My kids have have five singers they have
on repeat
forgotten the other two.
Dr Viviane Richter (18:05):
So, they're your favourite?
Associate Professor Kishore Kumar (18:06):
They're not my favourite bands. But this is all that
we listen to in the car. Yeah.
Dr Viviane Richter (18:11):
Do you have a favourite quote or life motto that
resonates with you?
Associate Professor Kishore Kumar (18:16):
Actually, I really think never giving up and persisting despite
all the challenges that you might face. Working really hard
and and being kind to people and polite to people
and respectful. And I think this is really important because
clinical work and research, it can be very stressful. And
I think we should all treat each other really politely
(18:36):
and respectfully and try to support each other through a
very challenging career.
Dr Viviane Richter (18:42):
What's your favourite way to get exercise?
Associate Professor Kishore Kumar (18:45):
So, I, I just go to the gym and run
on the treadmill. This is a bit boring. But in
the Parkinson's, uh, meeting in Philadelphia, and every year, we
have an international Parkinson's meeting and there's a five kilometre run.
And I'm determined to do well at that five kilometre run,
and run it alongside other neurologists and, uh, hopefully I'll
be able to finish in a reasonable place. So, that's
(19:08):
that's my goal. I'm working towards this run at the
Parkinson's meeting.
Dr Viviane Richter (19:12):
What's the current book you're reading?
Associate Professor Kishore Kumar (19:14):
Uh, the current book I'm reading is called Unruly by
David Mitchell, and it's a take on the on British history.
And we're really fans of David Mitchell from his comedy
work on the BBC and uh, all the great shows
that we watch. So, I'm looking forward to reading this book.
Dr Viviane Richter (19:30):
Who inspires you the most?
Associate Professor Kishore Kumar (19:32):
Well, I'm obviously, I'm inspired by my wife. And I'm
not just saying that, but she's just an amazing person.
She puts up with me quite a lot with this,
with working so much late hours. But she's an inspirational person,
and she is a dentist, and she also works with
the university and does her own research. And she's an
inspiration to me. My family, my daughters are also amazing
(19:55):
little humans who inspire me as well. At work, I'm inspired
by some amazing mentors. Professor Carolyn Sue, who was a
mentor for my research, and Professor Christine Klein, who's just
an amazing researcher in Germany who I did my PhD with.
And I work with such amazing scientists around the Garvan, like Ira Deveson.
(20:17):
I'm working with scientists in at Concord, uh, Marina Kennerson. So,
I've got so many amazing people to inspire me and
great mentors in my life. So, I'm very lucky.
Dr Viviane Richter (20:27):
Associate Professor Kishore Kumar, thank you so much for joining
us on Medical Minds.
Associate Professor Kishore Kumar (20:32):
Thank you so much, Viv.
Dr Viviane Richter (20:34):
If you'd like to know more about Kishore's research or
donate to the work we do at Garvan, head to garvan.org.au.
Garvan is leading the Australian Parkinson's Mission, which is currently
recruiting trial participants. This is one of several research programmes
at Garvan investigating Parkinson's disease. If you or someone you
know is interested in participating, please visit this website
(21:02):
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening. This podcast was recorded on the traditional Country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.
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