Kathleen Shannon, M.D., a neurologist at Rush University Medical Center in
Dr. Shannon: Huntington's disease is a hereditary disease that affects every
generation of a family. There are three types of symptoms. There is a movement
problem -- difficulty making movements and then movements are contaminated
by extra or involuntary movements and that includes walking, balance, etc. It
progresses and becomes very disabling. The second part is a behavioral
problem, and by that I mean depression, irritability, anxiety, sometimes difficulty
controlling the temper. Then the third part is a cognitive disorder, which is trouble
with planning, organizing, thinking, memory, ultimately resulting in a person who
really can't do anything for themselves in terms of physically or mentally.
What is chorea?
Dr. Shannon: Chorea comes from the Greek word for dance. That's where
choreography comes from, and it refers to the one specific type of involuntary
movement people with Huntington's disease have, where it's a writhing, kind of
rapid, purposeless movement. The severity of chorea varies quite a bit from
patient to patient. Some people have lots of it, and some people have relatively
little, so there are degrees.
How does having chorea affect a person's quality of life?
Dr. Shannon: One interesting thing about chorea is many patients with chorea
don't recognize they have it. I have one articulate patient who says that even
when she looks at herself in the mirror she doesn't see it. She can see it when
she watches herself on video, but she doesn't see it when she looks at herself in
the mirror, and she doesn't feel it; but it does interfere with movement in some
patients when it's severe, and patients who know they having chorea -- not that
the feeling it, but know that they have it -- may limit their activities. They may not
go to a restaurant or to a movie, so in that sense it does decrease quality of life.
It makes it harder to feed yourself and do those kinds of activities.
Prior to the drug tetrabenazine (Xenazine), what was done to treat chorea?
Dr. Shannon: There were no FDA approved treatments. There are medicines
that people had kind of tried over the years and with some success. Medicines
were often used to treat schizophrenia would be useful to control chorea. There
is an anti-Parkinson's drug called Amantadine that sometimes helps control
chorea, so it's been kind of a trial and error way of managing the symptom.
What is different about Xenazine?
Dr. Shannon: Tetrabenazine is more potent at controlling the chorea. Virtually
everyone with significant Chorea will have a response, whereas with other drugs
that we've used in the past, not everyone responds, and the response isn't
always as complete. So the tetrabenazine is a much more effective treatment for
How does it work?
Dr. Shannon: Chorea in Huntington's disease is related to an increased
sensitivity of the brain to the chemical dopamine, which is a you know, brain cells
use chemicals to communicate. The traditional medicines block dopamine's
effects in the nervous system. Xenazine depletes the nervous system of
dopamine, so instead of the dopamine being released and being blocked, it's
actually depleted so it can't be released, and for some reason that's more
effective than simply blocking the dopamine.
Are there any side effects of depleting dopamine completely?
Dr. Shannon: Yes. Powerful medicines have powerful side effects. This is not for
sissies, this drug. It can cause significant depression. It causes people to feel
slowed down or sluggish. It can cause people to be sleepy, so it can be difficult to
use. The trick for using the drug is to start it at a really teeny tiny dose and
increase it very gradually and keep in pretty constant contact with the patients to
make sure everythings going okay.
Is this the kind of drug that you kind of have to evaluate on a patient to
patient basis; you want to make sure that the benefits outweigh the risks?
Dr. Shannon: Exactly. You can't tell ahead of time so much. if a person has a
history of depression, that might not be a very good person to try on
tetrabenazine, but you can't always predict, so that's why you need to really have
a system for the patient being able to phone and talk to someone and report how
they're feeling so that the dose can be adjusted. In between visits to the office,
for example, you need to keep in really close contact with patients.
What do the results from the clinical trial show in terms of how effective the
Dr. Shannon: It was significantly effective; really substantial improvements in the
presence of chorea and how severe it was when it happened; but it did have side
effects. There was a suicide in the study in a person that wasn't thought to be
suicidal, and there was depression in the study and sleepiness, so again, it's a
really powerful drug with powerful side effects.
Even though this drug isn't a cure for Huntington's disease, why is this
drug so important for people suffering from it?
Dr. Shannon: It's important for people to understand that the Huntington's
disease has many, many symptoms and chorea is the only one. This treatment
actually doesn't improve anything except chorea, and in fact, in the study, some
things were a little bit worse. The functional state, how well people were able to
care for themselves was a little bit worse, and thinking and memory was a little
bit worse, and mood was a little bit worse, and so that speaks for making certain
that you evaluate the risk to benefit ratio individually in each patient. People with
Huntington's disease are very anxious for any new treatment, particularly if it's
something that would be a cure for the disease. This is not a cure. It simply
covers up one of the symptoms of the disease, but when you have an incurable
disease, anything that improves your quality of life is a welcome addition to the
pharmaceutical armamentarium, so anything that makes people able to go to a
movie or to go out to a restaurant with their children is an important thing for
Have you seen a significant improvement in Mary Born?
Dr. Shannon: She's been on tetrabenazine for a while. She's been getting it from
Canada and before that from Ireland, I believe. She was someone who really
didn't want to go out. She wanted to not be seen in public because she was
concerned about the way that she looked, and once she started on
tetrabenazine, she was able to go out and be in public again, so for her that was
a really important thing.
Patients with Huntington's disease have the verbal and motor skills
changes, but do they mentally still understand everything that's going on
around them and understand their condition?
Dr. Shannon: It can be hard to know how much people understand because
people with Huntington's have trouble expressing their feelings. They have
trouble coming up with the right words. They do lose cognitive function
progressively from early on in the disease. They lose the ability to express their
feelings, to plan things, to organize things, to multi-task and so it can be difficult
to know how intact they are, but unlike something like Alzheimer's disease, their
memory and other aspects of thinking are preserved for a relatively long time.
They don't lose memory function until relatively late in the disease. It's mainly
really high level thinking.
Is Mary's case not as severe as other Huntington's patients?
Dr. Shannon: No, I don't think that that's the case. Actually, you don't see chorea
because she's medicated to stop the Chorea, but she's had a lot of changes in
her life. She has got a good family and she's a good person and so she copes
better than many people would, but she's got significant impairment and
What's on the horizon for Huntington's disease?
Dr. Shannon: There's a lot of interest in Huntington's disease, because we have
the gene. You can put the gene in animals and get a good model of the illness.
It's fairly easy and quick to test treatments, so there are a number of things that
have been identified in animal studies that look like they'd be easily tolerated in
people, and that would be easy to give to people, and might potentially slow
down the degeneration of the disease and therefore slow down the progressive
worsening our patients have. We're currently enrolling research subjects into a
large study of co-enzyme COQ-10, which is a health food supplement that is
showing some preliminary evidence that it might be useful. There's interest in
high doses of creatine, which is another health food supplement. This is an
orphan disease and because it's an orphan disease, there are not a lot of drug
companies lining up to invent new treatments for Huntington's disease, so to
have even two clinical trials like this is really exciting for us, and really exciting for
our patients -- new things that we hope might slow disease progression.
What's is the definition of an orphan disease?
Dr. Shannon: Less than 200,000 people affected, I think, is the current
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe
Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the
depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult
your physician on medical matters.
If you would like more information, please contact:
Kathleen Shannon, MD
Rush University Medical Center