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Welcome
Welcome to Issue 11 of NA News, the periodical dedicated to
bringing researchers, patients and research sponsors up to date
with the latest news about neuroacanthocytosis (NA) related
diseases, a rare group of diseases affecting the brain. NA News is
part of our coordinated effort for better information and
scientific exchange about these conditions, which, while rare, bear
similarities to and can shed light on common neurodegenerative
disorders such as Alzheimer's, Huntington's and Parkinson's
diseases.
In this issue we are honoured to announce the launch of the
long-awaited Neuroacanthocytosis Patients’ Registry, a
groundbreaking new reference tool for NA clinicians and
researchers. We also report on the excellent response to the Fourth
International Neuroacanthocytosis Symposium, and we welcome our new
liaison for French-speaking patients and families. You'll also find
our latest Research Update, Patient News and Fundraising Roundup.
Please forward NA News to anyone who may find it of interest. You
can always find the latest issue online at http://www.geocities.com/nanews2003/
where you can add a friend to the list or unsubscribe from the
publication in the area marked "Join or Leave NA News" or on our
own website at www.naadvocacy.org where a Japanese
translation as well as past editions can be found.
Fourth Symposium bridges clinical/research gap
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| Prof. Edmund Critchley (left) and
Prof. Anthony Monaco |
The Fourth International Neuroacanthocytosis Symposium this
past July illustrates the key developmental stage NA research has
now reached: dialogue and information exchange among clinicians and
researchers is strong and growing, and the diversity of attendees
proved just how attractive NA research is becoming to a broader
community of specialists, from fields including cell biology and
genetics.
Supported by the Advocacy and organised by Antonio Velayos-Baeza,
PhD, the Symposium was privileged to have as guest of honour Prof.
Edmund Critchley, an NA pioneer who helped establish the diagnosis
in medical literature. NA was originally described as
Levine-Critchley syndrome following Critchley's two encounters with
symptomatic patients in the 1960s, one in the US and the other in
Lancashire in the UK. The patients both conformed clinically to the
typical picture of autosomal recessive chorea-acanthocytosis (ChAc)
as now defined by mutations of the VPS13A gene.
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| Prof Adrian Danek and Prof
Alexander Storch |
Subtitled "Bridging clinical and basic aspects," the Fourth
Symposium did exactly this, addressing the connections between, and
the pathogenesis of the NA syndromes chorea-acanthocytosis (ChAc),
McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and
neurodegeneration with brain iron accumulation (NBIA). Opening with
a day-long review of the clinical features of the syndromes
organised by Susanne Schneider, MD, Day One at The Institute of
Neurology, London was chaired by Prof. Kailash Bhatia and Dr.
Richard Hardie, and also featured Dr. Patricia Limousin's round
table on the application of deep brain stimulation.
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Prof. Edmund Critchley, Prof.
Bernhard
Landwehrmeyer and Dr Akira Sano |
Tackling the basic science aspects of NA syndromes, Day Two
opened at the Department of Pharmacology, Oxford, chaired by Prof.
Anthony P. Monaco, Head of the Neurogenetics Laboratory at the
Wellcome Trust Centre for Human Genetics, University of
Oxford. Potential roles for VPS13A were examined in the model
organisms yeast and tetrahymena, and include a potential function
in phagocytosis, which has recently been proposed to be involved in
the pathogenesis of a number of neurodegenerative conditions.
Processes involved in red cell membrane shape and physiology were
reviewed, with an emphasis on the limited understanding of the
proteins which are prominently involved in the cell shape changes
of the NA syndromes, including those which make it remarkably
deformable under normal circumstances.
The symposium was endorsed by The Movement Disorder Society and
was supported by The Institute of Neurology, London; The Brain
Research Trust, London; The National Hospital for Neurology and
Neurosurgery, London; The Wellcome Trust Centre for Human Genetics,
Oxford; Glaxo Smith Kline; and Livability (John Grooms/The
Shaftesbury Society).
In addition to the Advocacy, the members of the Organizing and
Program Committees were Benedikt Bader, Germany; Kailash Bhatia,
UK; Adrian Danek, Germany; Sonia Gandhi, UK; Glenn Irvine, UK; Hans
H. Jung, Switzerland; Clotilde Levecque, UK; Anthony P. Monaco, UK;
Susanne Schneider, UK; Antonio Velayos-Baeza, UK, and Ruth H.
Walker, USA.
Our thanks goes to all attendees and supporters. Watch NA News for
updates on research progress as we move toward the Fifth Symposium.
NA Research moves to a new level with debut of patient database
A wealth of anonymised NA case information is now available online to authorised
researchers following the final release this autumn of the
Neuroacanthocytosis Patients’ Registry. Launched in October
on the website of the European Huntington Disease Network, the
registry includes the latest updates to several scales which will
assess the outcome of deep brain stimulation therapy in
neuroacanthocytosis patients, which was done in partnership with
Prof. Dr. Lars Timmermann from the University of Cologne in
Germany.
The database was released to a limited number of physicians caring
for ChAc patients in early October and by the end of October the
first sets of patients were entered. Physicians caring for patients
suffering neuroacanthocytosis syndromes worldwide are being
continuously contacted to expand the database. The case reports are
pseudonymous and only available to qualified professional
researchers.
A public section of the database internet homepage at www.euro-hd.net/html/na/submodule
provides useful information about NA. Future use of this
database mainly focuses on comparison between existing therapies
and the evaluation of new therapeutic strategies to improve the
efficacy on one hand and to increase the number of options on the
other. We expect that the comparison of the development of the
diseases and the outcome of therapies such as deep brain
stimulation will lead to an improvement of the quality of life of
all neuroacanthocytosis patients.
The international database was conceived in 2003 by Adrian Danek
to allow researchers around the world to have ”virtual”
experience of many more cases than would ever be found in one
hospital or indeed one country. Patients and their families can
promote research by encouraging their neurologist to enter their
cases on the data base by contacting Adrian Danek at [email protected] or Benedikt
Bader at [email protected]
MRI scans could assist ChAc diagnosis
Results of innovative work at an Australian clinical/research
centre suggest that clinicians may be able to begin using MRI scans
to correctly diagnose ChAc.
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| Katie Kotschet, Dr. Anthony Hannan
and Dr. Mark Walterfang |
Using expertise in structural imaging, and the application
of shape analysis to brain structures, Dr Mark Walterfang from the
Melbourne Neuropsychiatry Centre was able to examine the size and
shape of the caudate nucleus in 15 scans from patients with
chorea-acanthocytosis, and compare these to scans from matched
controls and matched patients with Huntington's chorea drawn from
the Centre's imaging database.
The group at MNC demonstrated not only significant differences in
size of these brain structures in patients with ChAc compared to
Huntington's Disease, but also key differences in shape. Given that
Huntington's Disease is one of the key differential diagnoses in
cases of ChAc, these findings should assist clinicians in correctly
diagnosing ChAc from MRI scans.
Headed by Professor Christos Pantelis and Dr Dennis Velakoulis,
the Melbourne Neuropsychiatry Centre specialises in combining
structural and functional imaging with neuropsychology and
behavioural neuroscience. It has developed strong research streams
in schizophrenia and allied disorders, adolescent and early adult
neurodevelopment, addiction neuroscience and research into uncommon
neuropsychiatric disorders.
NA Advocacy reaches out to French speaking patients
The Advocacy is delighted to welcome Anne Depaulis, who has joined
us in our drive to communicate with as many patients worldwide as
possible in their own language.
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| Anne Depaulis |
Anne will correspond with all French speaking NA patients
and their families and can be reached directly at [email protected] Born
in France and now residing in Geneva, Anne is truly international;
she started her travels in America, where she was an exchange
student, and subsequently relocated to London and Hong Kong for
business; she is a personal friend of the Irvine family. Don't
hesitate to contact Anne directly with any queries or comments en
français. Louise Dreher at [email protected] continues to make
a valuable contribution as advocate for German speakers.
NA in knowledge exchange with Huntington's Disease Network
Here at the Advocacy for NA Patients we were fortunate to attend a
key event in September for researchers and support groups for
Huntington's Disease, a rare condition that, symptomatically,
closely resembles NA.
At the kind invitation of G. Berhard Landwehrmeyer, president of
the European
Huntington's Disease Network, Glenn and Ginger Irvine attended
the network's 5th Annual Plenary Meeting in Lisbon from 5-6
September 2008. The event was exceptionally well attended, with 250
people expected but close to 500 attending. Clinicians, scientists,
fundraisers and representatives of country support groups met to
discuss recent research, results of working group activities and to
foster the feeling of inclusivity of all people affected by this
rare disease.
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| Ruth Walker's "The Flow Chart for
the Diagnosis of Chorea" at the Fourth
Symposium |
HD is a rare autosomal dominant disease that is more common
than NA. As NA most closely resembles HD symptomatically, it
behooves us to pay attention to the evolution of the European
Huntington's Disease Network, both as a support group and in terms
of research advancements. Also discussed were some therapies as
they have been tried with HD patients.
Many posters were displayed including NA researcher Ruth Walker's
"The Flow Chart for the Diagnosis of Chorea". Ruth's work drew much
admiration and allowed us to explain both the NA group of diseases
and how our two organisations might be mutually beneficial by
sharing ideas and processes.
The European Huntington’s Disease Network (EHDN) is a truly
impressive group founded in 2006 that brings together clinicians,
research scientists and patients’ advocacy organisations
around Europe in the drive to discover a therapy that will relieve,
retard or stop Huntington’s Disease. EHDN is closely
associated with the CHDI Foundation Inc., a powerful international
network of research laboratories from academia and industry
pursuing novel ways to treat HD with drugs and doing it as quickly
as possible.
A central tool of the EHDN is a Huntington's Disease case database
that will aid future research. As described elsewhere in this issue
("NA Research moves to a new level"), Ludwig-Maximilian's
University in Munich has used this facility to create a specialised
neuroacanthocytosis case database. We are grateful to the
EHDN and hope to find opportunities to share both scientific and
therapeutic insights with them.
PATIENT FOCUS
Ed Ayala...Pete Clark...Alex Irvine
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| Ed Ayala |
Ed Ayala writes to tell us about his early success
with the Palmtop3 by DynaVox
Technologies, a handheld device that "speaks" words, phrases and
sentences, and so makes it easier to communicate. Ed says he's been
able to create phrases and questions, as well as use preprogrammed
material on the device. Despite early difficulty, Ed says he's
getting there. "I still have a lot to learn about my new friend,
but for now it has made a huge difference," he writes. "I can use
it as a backup whenever someone does not understand what I am
trying to say. Unfortunately this is happening more often than
not."
For Ed, speech has been the aspect of life most affected by NA,
followed by chewing and eating. His loss of clear speech, he says,
left him feeling low and increasingly withdrawn. "I became
extremely introverted, frequent phone calls to family and friends
began to stop. I knew what I wanted to say but what came out would
be slurred or mumbled. It became more and more difficult for me to
communicate with friends, family, and co-workers. Speech therapy
was helpful but I needed something else, something I could use as a
backup when I was not understood." So far, he says, the Palmtop3
seems to be a good backup. "My wish is that with lots of practice
on the device, I can regain my confidence and self esteem. On a
side note while serving in the U.S. Army I was a communications
specialist -- talk about ironic!"
Pete Clark, another NA patient struggling to cope with the
painful and difficult symptoms of this disease, writes to tell us
of a new outlook he has tried to adopt as his physical abilities
retreat. "I am slowly beginning to learn to think in terms of what
I have achieved in a day, rather than the long list of things I
could have done in the past – reducing my expectations also
reduces my levels of stress," he says. "Taking things more slowly
definitely improves the clarity of my speech and the quality of my
handwriting. I recently went to an exhibition of local woodworkers
and this has inspired me to renew my efforts at woodcarving."
Like many others, Pete experiences increasing difficulty with
eating and movement. "Mealtimes can be slow and messy," he says. "I
do admit to enjoying cake, which goes down a treat when moistened
with milk. Ever since my walking has been getting worse it has
restricted my mobility and I have been using the wheelchair much
more (I feel that the bumpy ride just shows the poor state of our
pavements); this is just a minor point as my mobility has improved
so that I can now get around the shops without falling over!"
Pete also offers the insight that his mouth is "much more active
during thunderstorms – is anyone else affected in a similar
way?" Write to us here at NA News or share your thoughts in the
Patients' Yahoo Group at http://health.groups.yahoo.com/group/Neuroacanthocytosis/
|
| Alex Irvine with her lovely cat,
KC |
In London Alex Irvine would like to convey her
thanks to the many friends and relatives who have contributed to
the NA cause and who have communicated with her throughout the last
year. She has made a remarkable recovery from her knee replacement
surgery in March and now is more confident in moving around the
house. She was able to visit friends in Boston, Massachusetts in
June and is proud of her finished embroidery.
When Alex was bothered by copious drooling this autumn, her doctor
prescribed scopoderm, a patch often used to prevent motion sickness
which has been of help. She has been receiving physio, speech and
occupational therapy support from her local council which has
encouraged her to practice standing correctly, make better use of
her curled hand and introduced the idea of a Lightwriter voice
machine to help communication. This ongoing attention to the
day-to-day well-being of patients should be available to all
patients.
IN MEMORIAM
Mark Parry...Theo Koutsis
In memory of Mark Parry - a tribute by Fiona Maguire
"Life is a blessing. Not being born, and not dying at one's time,
these are great misfortunes." - Lie Zi, Zhou Dynasty
The Mark I knew and loved was always aware that life was for
living.
We met at Art College in Dundee just over 20 years ago. We were
together there, and subsequently in Edinburgh for 11 years. This
tribute is about remembering Mark at his best. He was tall, dark
and handsome with a sunny personality; confident, happy and full of
life. Never far from his guitar, whether playing in bars or busking
on the street, Mark loved an audience. But mostly, he just loved
music. To play his guitar and sing were his passions. Although he
chose graphic design as his profession, I often wonder what would
have happened if he had followed a musical path instead.
Mark loved to laugh and had an idiosyncratic sense of humour which
would have got most people into trouble but somehow everyone
accepted Mark as he was. I have so many memories of Mark with
friends laughing till we cried. He had a "Peter Pan" quality, which
never left him. Mark had a lot of friends and made friends easily
wherever he went. His longest and best friend, Ian, was close to
him right to the last.
Mark unfortunately had to face so many difficulties with epilepsy,
NA and the loss of his sister Sian and brother Dave. In spite of
his degenerative condition and his suffering in the last few years,
Mark knew how lucky he was to have the unconditional love of his
parents Gill and Gordon.
None of us ever know how long we will be for this world and Mark's
time was certainly cut cruelly short. But in his time, Mark touched
many people's lives and I was lucky to have been one of those
people whose life he touched the most.
Fiona Maguire
The Strathearn Gallery,
Crieff, Scotland
In memory of Theo Koutsis
The family and friends of Theo Koutsis are saddened to report his
passing in Melbourne, Australia on 28 February 2008. Theo was a
typical Melbournian: football-mad, with an infectious smile, a
laconic sense of humour and happy-go-lucky personality and always
putting others' needs before his own. Theo had involvement with the
Neuropsychiatry Unit at the Royal Melbourne Hospital for
approximately 5 years. In memory of his passing, the Greek
community in Melbourne raised AUD2,240 for the Melbourne
Neuropsychiatry Centre, who are conducting neuroimaging research on
chorea-acanthocytosis and comparing brain regions with sufferers of
other basal ganglia disorders such as Huntington's disease. The
results of this work were presented at the Fourth Symposium in
July.
RESEARCH UPDATE
Dr. Antonio Velayos-Baeza and Prof. Anthony P. Monaco
Wellcome Trust Centre for Human Genetics, University of
Oxford, UK
The objective of this project is to obtain antibodies against the
four members of the human VPS13 protein family. VPS13A is altered
in chorea-acanthocytosis. This will not only improve specific
diagnosis, but also be vital to determining the location and
function of these proteins in healthy individuals and thus lead to
therapies that will correct or replace the function of the mutated
proteins.
We have performed the first three of five steps. By testing
protein segments in bacteria we have selected 3 fragments from each
protein. Next we have to make the protein segments soluble. We
should have the first protein fragments ready this month. The
fragments will then be used for the immunisation of animals that
will produce the antibodies. We will have antibodies against these
fragments between 3 and 5 months later.
At that point we will characterise them and select those that work
for different applications (immunofluorescence, immunoblotting,
immunohistochemistry). At the end of this research project we
expect to have a panel of antibodies that can be used to detect all
the VPS13 proteins.
Benedikt Bader, Adrian Danek
Diagnostic testing for Chorea-acanthocytosis (ChAc): Since 2005
156 samples of suspected patients and 42 controls were sent for
analysis. In total, 55 (35%) patients were diagnosed with ChAc.
There was a large increase in samples in the first quarter of 2007
following an important article by Ruth Walker et al. appeared in
the prestigious journal Neurology. As technical experience grew,
the mean time between sample receipt and final diagnosis was
reduced from 9 months in 2005 to 9 weeks in 2008.
Prof Giel Bosman PhD
Neijmegen Univesity
Netherlands
The first year’s work:
- succeeded in setting up a reliable, robust methodology for
determination of the proteome (i.e. protein composition) of
the red blood cell plasma membrane, that is suitable for a
comparative analysis of multiple samples as planned for the
second phase of the project.
- using this method discovered that the membrane protein
composition of two different NA patients indicate a common change
in the band 3-ankyrin complex.
This data, together with material presented at the Fourth
Symposium in Oxford and a newly developed biophysical model for red
blood cell membrane stability, may lead to a molecular
identification of the mechanism of formation of spiky red blood
cells.
Lucia De Franceschi MD
Associate Professor of Internal Medicine
Department of Clinical and Experimental Medicine,
University of Verona, Italy
In the first year, we carried out systematic analysis of the
proteome (protein composition) from red cell membranes of normal
and of ChAC erythrocytes (red blood cells) identifying proteins
that are differently expressed. Since no data are available on
systematic analysis of the red cell membrane proteome of ChAC
erythrocytes, we had to carry out this analysis to evaluate whether
morphological and functional differences between normal and ChAC
red cells were related to quantitative and/or qualitative
differences between the red cell membrane proteomes. The identified
proteins are not only descriptive data, but they also indicate that
the major differences between red cell membrane proteomes are
related to possible post-translational modifications in the
protein. In fact, the preliminary data on the phosphotyrosine
proteome supported this observation.
Now, we plan to complete the analysis of the phospho-tyrosine
proteome in normal and ChAC red cells as well as on MLS
erythrocytes. The phospho-data will be then used for computational
analysis of phospho-networks in order to identify novel signalling
pathways to be validated in diseased red cells. This strategy will
allow us to highlight new potential regulatory mechanisms to be
validated as markers in disease pathophysiology this may also be
useful to clinical practice in patient diagnosis or follow-up.
FUNDRAISING UPDATE
Run and jump for NA
We are tremendously grateful to the individual and corporate
sponsors who help support NA research. The Advocacy's work would be
impossible without the substantial donations from The Carlbetz
Foundation, The Blavatnik Charitable Foundation, the
J. Macy Foundation, and the Mary Kinross Charitable
Trust. We also thank Glaxo Smith Kline, which gave
important support for the Fourth Symposium in July 2008.
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| Camille Cook |
The sponsorship work of individuals is especially precious
to us, and we are continually inspired by those of you who are
personally committing yourselves to helping the patients and
families affected by NA. With your help, NA research will progress
-- and, we believe, may also contribute to the understanding of
Alzheimer's, Huntington's and Parkinson's diseases.
This issue our thanks go out to all the many runners and parachute
jumpers who are literally going the extra mile to support NA! We
send hearty thanks to Camille Cook,
the Assistant Minister at St Columba's Church in London who
traveled to Atlanta, Georgia to run her first ever marathon, a
42-kilometer race on Thanksgiving Day. Supporting Camille is easy
and quick to do - just log on today and give what you can at http://www.justgiving.com/camillecook
Also in the UK, Andrew, Chantal & Sam from the real
estate desk of the leading executive search firm, Whitehead Mann,
completed the 16-kilometer Great South Run around Portsmouth on
October 26 for NA. Their sponsorship page remains open, so there's
still time to support their huge effort on behalf of NA -- just log
on at http://www.justgiving.com/realestateinarealstate
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| Mark Over completed a parachute
jump, raising over STG200 for NA |
Mark Over, a friend of NA patient Mark Parry who
sadly died earlier this year, completed a parachute jump in the
summer as a tribute to Mark. He managed to raise over STG200 for
NA. Thanks from all of us who are so affected by NA.
We're also pleased to report that a mail distribution fundraising
effort in the UK helped raise more than STG5500 in October and
November. These funds, like the other help we receive, will be used
exclusively to offset the small operational and significant
research costs of the Advocacy.
We're delighted to give you a further report on Chris
Hamilton of Portland, Oregon, who we introduced in the last
issue. Chris's sponsored "April for Alex" walk was a great success:
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| Chris walked over 80 miles,
collecting over USD3000 for NA |
Chris walked more than 80 miles and collected over USD3000
for NA (http://aprilforalex.blogspot.com/).
Many thanks, Chris!
Donations may be sent to the Advocacy for Neuroacanthocytosis
Patients, 32 Launceston Place, London W8 5RN, UK. Please do contact
us for the appropriate account to pay depending on your currency,
by emailing either Ginger or Glenn Irvine.
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