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					euro-                                       european
                                            federation of
                                                                                    Newsletter No. 19

                                                                                      December 2000
ATAXIA                                      hereditary ataxias

EDITORIAL                                                                                   CONTENTS

Michael Morgan                                                               Editorial ........................................ 1

                                                                             Recessive ataxias: medical and

M     any people, it seems, are getting just a little impatient with the
      seeming lack of progress in developing therapeutic treatments for
ataxia. With the initial cloning of the FRDA gene in 1996 and the subse-
                                                                             scientific update ........................... 2

                                                                             Dominant ataxias: medical and
quent unravelling of its biochemical basis a mere year later it was          scientific update ........................... 4
thought that effective treatments if not ‘just around the corner’ were
                                                                             ‘Biloxi Blues’................................. 8
none the less within grasp. But nothing much seems to have came on-
line. Possibly scientific research was focused so much on discovering the    ‘Drunk as a skunk’........................ 8
gene that what came after was bound to be something of an anti-climax.
But a lot is happening, though it’s on a longer timescale and involving      More than just medical ................. 9
the boring but necessary ritual of scientific experimentation and testing.
                                                                             Accepting help ........................... 10
Inside Michel Koenig presents a summary of the current state of play in
research into FRDA and other recessive ataxias.                              The Gift ...................................... 10
And no, we haven’t forgotten dominant ataxia either. Ewout Brunt pro-
vides us with an update on these ataxias.                                    New FA Association in
                                                                             Switzerland ................................ 11
More and more ataxic people from Europe are journeying out to the USA
to attend the National Ataxia Foundation’s annual conference. It’s good      Members & contacts .................. 10
to see that this three day event has become an important feature in the
ataxic year world-wide. Last year I myself went, and I met fellow Euro-
peans Peter Reussner and Cornelia Karg there too. This year it was Jon
Bunnig and Nicola Böhme’s turn to fly the flag for Euro-Ataxia when
they attended this year’s NAF conference in Biloxi, Mississippi. Inside
Jon writes frankly on his experiences there. Those of a nervous disposi-
tion have been warned!
Anybody with experience of FA knows very well what its like to be ac-
cused of drunkenness. God knows its happened to me often enough –
even when it wasn’t true! Inside Lieuwe Koopmans gives a humorous ac-                             Editor
                                                                                           Michael Morgan
count of what happened to his son Erik when he visited different bars.                      2 Glenhill Park
One was in the Netherlands – and the other was in Ireland. Slainte!                           Glen Road
Is FA or any other ataxia merely a medical problem with no other level                    Belfast BT11 8GB
                                                                                           Northern Ireland
of experience? Doctors and other medical people are prone to see the                    Tel: +44 2890 302944
ataxic person as only a ‘patient’ but anybody with ataxia knows that                    Fax: +44 2890 302973
having ataxia is a much more complex reality. These issues came to my          E-mail:
mind during last year’s Westende Conference, and inside I return to the
theme, to try to probe these matters at greater length.                                    Carolien Koopmans
This is the last Euro-Ataxia Newsletter this millennial year. The 2000                         Hans Doré
AGM in Sweden at the end of September promised to be a well organised                       Marco Meinders
and informative Conference and it was. Next years AGM, in 2001, will
be held in Edinburgh, Scotland. At this early stage details are yet to be
                                                                                                 Lay out
                                                                                               Hans Doré
worked out but the canny Scots have provisionally booked the weekend                    Mina Krüseman-erf 131
21-23 September. Plenty of craic and I hope to see you all there.                       NL-3315 GE Dordrecht
Coming soon to a screen near you – a video centred on FRDA. Wellcome                     Tel: +31 78 6212110
Trust and EIBE – European Initiative in Biotechnology Education – are                    Fax: +31 78 6215287
planning to produce multi-language versions of ‘The Gift’, translating it               E-mail:
from its original English into Spanish. German, French, Italian and
No. 19 – December 2000                                                                               EURO-ATAXIA

Dutch copies. The Gift is a play trying to “raise           an e.
awareness of genetic selection and the ethical impli-
cations it could play on peoples lives,” as it’s produc-    Finally the Swiss have arrived. See inside for Daniela
ers UK Welcome Trust put it. If you can’t wait and          Iser’s introduction to aCHaf, the new Swiss FA asso-
want to watch the English-language version drop me          ciation.


Michel Koenig

F    ew forms of recessive ataxias have been recognised
     so far. The most frequent form (in Europe and in
populations with European descent) is Friedreich’s
                                                            tion’s have submitted for publication. On the other
                                                            hand, the identification in 1996 of the gene defective in
                                                            Friedreich’s ataxia has prompted a lot of work to un-
ataxia, which was described as early as 1863 by             derstand the mechanism of the disease, construct
Nicholaus Friedreich. The second most frequent form,        mouse models and design tentative therapies. Fried-
ataxia telangiectasia, was not reported until 1921 and      reich’s ataxia is caused by a GAA trinucleotide repeat
was only fully described after 1945. Other forms of re-     expansion located from outside the coding region of the
cessive ataxias are much rarer and were recognised          gene. For this reason, the encoded protein, which we
still later. These include Refsum disease, abetalipopro-    named frataxin is of normal size but is produced in
teinemia, ataxia with isolated vitamin E deficiency         very reduced amounts due to the expansion mutation.
(AVED), spastic ataxia of the Charlevoix-Saguenay           We have shown in a mouse model that having no fra-
(RSACS) and infantile onset spinocerebellar ataxia          taxin at all is lethal very early in embryonic develop-
(IOSCA).                                                    ment. The disease in patients is therefore the conse-
                                                            quence of having very small amounts of the normal
Some of these rare recessive ataxias are more frequent      frataxin protein. Four years after its discovery, the
in particular regions of the world, such as North Africa    function of frataxin still remains elusive. The sugges-
for AVED, Western Quebec for RSACS and Finland for          tion that frataxin might serve as a transporter of iron
IOSCA. This geographic patterning also allowed them         in or out of mitochondria, a small subcellular struc-
to be recognised and genetically located (on a chromo-      ture, is the centre of active controversy among the sci-
some). All of them, except IOSCA, also had their gene       entific community. A paper published in September
identified during the last 5 years, the latest newcomer     (Adamec et al. 2000) shows that frataxin can assemble
being RSACS (Engert et al. 2000). The RSAC gene is          in a multisubunit structure that forms a shell around
coding for a large protein of unknown function. Most        an iron store, presumably to protect the cell from the
Quebec patients have the same mutation and the mu-          toxicity of excess of iron. However, this multisubunit
tation status for patients with other geographic origins    assembly only seems to occur at high iron concentra-
is presently unknown. Due to the large size of the          tions that do not normally exist in living cells. Moreo-
RSACS coding region, it is not yet clear what will be       ver, two other papers published in July and October
the best molecular diagnostic strategy of non-Quebec        (Musco et al. 2000, Dhe-Paganon et al. 2000, respec-
RSACS patients. Ataxia telangiectasia (AT) is in a          tively) and reporting the structure of frataxin, i.e. its
similar situation, though the diagnosis of AT is accu-      three dimensional folding, indicates that frataxin does
rately performed by biochemical tests rather than by a      not bind iron. Only time will solve this controversy.
molecular test. Many other forms of rare recessive          What do we know about frataxin and the consequences
ataxias have been reported but they will be more            of its almost complete absence? Frataxin is a protein of
clearly recognised when their gene localisation will be     the mitochondria and some mitochondrial proteins are
identified, because it will allow to compare patients or    secondarily defective in affected tissues of Friedreich’s
families from different countries and having similar        ataxia patients. These proteins contain iron in so-
gene defects. This is what we have recently achieved        called iron-sulphur centres and many of them are part
for three forms, mostly thanks to documented consan-        of the mitochondrial electron transport chain, which is
guinity which is often found in rare recessive diseases.    involved in the major function of mitochondria, i.e.
The three forms of recessive ataxias are ataxia with        produce energy (ATP) for a cell. Iron and Coenzyme-Q
oculomotor apraxia (AOA, early onset form, at around        10 are the direct transporters of electron in this chain.
5 years of age, range 2 to 15), ataxia with elevated al-    How does it work? Electrons are transferred simulta-
phafetoprotein and elevated immunoglobulins (onset          neously from end products of food to oxygen (O2) to
around 20 years of age) and ataxia with hearing and         yield 2 molecules of water and release energy for ATP
visual (optic atrophy) impairments. The genetic and         synthesis (fuel for the cell). If only one electron leaves
biochemical description of the first 2 forms have been      the chain too early and encounters oxygen, it will re-
published or are in press (Barbot et al. in press; Wata-    sult in the formation of O2. – called superoxide ion or
nabe et al. 1998; respectively) and the genetic localisa-   anion – an oxidant molecule toxic for most neuronal

EURO-ATAXIA                                                                                 No. 19 – December 2000

cells. Free iron is also known to be able to produce su-    to the occurrence of the disease in the affected tissues,
peroxide ions by transfer of one electron to oxygen. It     as in the human disease. However, mitochondrial iron
seems today (but it is not yet definitively proven) that    accumulation and deposits were not seen in the ‘neu-
the iron-sulphur proteins are defective because of a        ronal’ mice (presumably because they died too early)
primary production of oxidant molecules (also called        and were seen in the heart of the ‘muscle’ mice only
free radicals, such as the superoxide ion) rather than      after the onset of the cardiomyopathy and after the oc-
to iron accumulation, as previously suggested. One          currence of iron-sulphur protein deficiencies. To us
way to protect cells from oxidant molecules is to use       this represents another argument which suggests that
antioxidant molecules. Vitamin C and vitamin E are          Friedreich’s ataxia is initially caused by free radical
antioxidant molecules, the first being soluble and the      production, which would in turn cause iron-sulphur
other being associated with biological membranes. Co-       protein deficiencies and then intra-mitochondrial iron
enzyme-Q 10, another component of the electron              accumulation (released from the defective iron-sulphur
transport chain, can also act as a membrane antioxi-        centres). If correct, this knowledge reinforces the ra-
dant. Idebenone is an analogue of Coenzyme-Q and            tionale of using antioxidants as a treatment directed to
can act both as a soluble and a membrane antioxidant,       one of the early steps of Friedreich’s ataxia pathology.
i.e. it is believed to be able to take the free electron    It will prompt us to test idebenone on our mutant mice
from a soluble free radical and bring it back to the        and check for any beneficial effect on survival and
electron transport chain (at the mitochondrial mem-         other parameters of the disease.
branes). For this and other reasons (Rustin et al.
1999), idebenone was chosen for a one year therapeutic      Adamec J, Rusnak F, Owen WG, Naylor S, Benson LM, Gacy
trial in two major hospitals in Paris (Hôpital Necker,      AM and Isaya G (2000) Am J Hum Genet 67:549-542
Pr Arnold Munnich and Hôpital de la Salpetrière, Pr         Barbot C, Coutinho P, Chorao R, Ferreira C, Barros J,
Alexis Brice). The results of the Salpetrière hospital      Fineza I, Dias K, Monteiro JP, Guimarães A, Mendonça P,
are not yet available (mostly adult patients) and only      Moreira MC, Sequeiros J (in press) Recessive ataxia with
preliminary analysis of the Necker results are avail-       ocular apraxia: review of 22 Portuguesse pati ents. Arch
able (Drs Pierre Rustin and Agnes Rotig, personal           Neurol
communications). The results were mostly obtained           Dhe-Paganon S, Shigeta R, Chi YI, Ristow M, Shoelson SE
with children. So far, the clearest beneficial effect was   (2000). Crystal Structure of Human Frataxin. J Biol Chem
seen on the cardiomyopathy, with a progressive reduc-       275:30753-30756 Engert JC, Berube P, Mercier J, Dore C,
tion of the hypertrophy (reduction of the heart walls       Lepage P, Ge B, Bouchard JP, Mathieu J, Melancon SB,
thickness), seen in most but not all patients. Some         Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A
subjective improvements were also noted on fatigue,         (2000) ARSACS, a spastic ataxia common in northeastern
dysarthria and fine hand movements (writing). No im-        Quebec, is caused by mutations in a new gene encoding an
provement was noted on gait ataxia and peripheral           11.5-kb ORF. Nat Genet 24:120-125
neuropathy. From the preliminary results, it’s not pos-     Musco G, Stier G, Kolmerer B, Adinolfi S, Martin S, Frenkiel
sible to confirm or exclude that idebenone is blocking      T, Gibson T, Pastore A (2000). Towards a structural under-
or slowing down the progression of these last two           standing of Friedreich’s ataxia: the solution structure of fra-
symptoms. An independent group has shown that ide-          taxin. Structure 8:695-707
benone reduces oxidative stress in Friedreich’s ataxia      Rustin P, Von Kleist-Retzow JC, Chantrel-Groussard K, Sidi
patients (Schulz et al. in press). In order to gain in-     D, Munnich A, Rötig A (1999). Effect of idebenone on car-
sights into the mechanisms of the disease and to try to     diomyopathy in Friedreich’s ataxia: a preliminary study.
get independent confirmation of the human drug trials       Lancet 354:477-479
(an important issue for drug approval and commercial        Rustin P, Munnich A, Rötig A (1999). Quinone analogs pre-
distribution), we have developed animal models that         vent enzymes targeted in Friedreich’s ataxia from iron-
somehow mimic the human disease. In order to avoid          induced injury in vitro. Biofactors 9:247-251
the embryonic lethality due to early complete absence       Schultz JB, Dehmer T, Schöls L, Mende H, Hardt C, Vorgerd
of frataxin, we thought to induce the mutation in our       M, Bürk K, Matson W, Dichgans J, Beal MF, Bogdanov MB
mice models after embryonic development and to re-          (in press) Oxidative stress in Friedreich ataxia patients.
strict the occurrence of the mutation in some tissues,      Neurology
namely neurons and muscle (including heart), with the       Watanabe M, Sugai Y, Concannon P, Koenig M, Schmitt M,
strategy called conditional knock-out. The ‘muscle’         Sato M, Shizuka M, et al (1998) Familial spinocerebellar
mice initially develop normally, then develop cardio-       ataxia with cerebellar atrophy, peripheral neuropathy, and
myopathy and die at about 10 weeks of age. The ‘neu-        elevated level of serum creatine kinase, gamma-globulin, and
ronal’ mice have induced mutations in many non-             alpha-fetoprotein. Ann Neurol 44:265-269
neuronal tissues, including heart, liver and thymus,
and they start to loose weight from birth onward and
die at about 3 weeks of age. In all cases we found (in
collaboration with the laboratory of Pierre Rustin) mi-
tochondrial iron-sulphur protein deficiency in parallel

No. 19 – December 2000                                                                               EURO-ATAXIA


Ewout Brunt

T   his update is based on the presentation during this
    year’s AGM in Valjeviken rehabilitation centre,
beautifully situated on the south coast of Sweden.
                                                             found in SCA3.
                                                             Very recently, in October, the gene mutation of SCA10
                                                             has been published by the same collaborating group
In last year’s update on dominant ataxia’s (Euro-            from Houston and Los Angeles who described SCA10
Ataxia Newsletter 18, Febr. 2000, p. 7-8), I could men-      last year in two Mexican-American families. As they
tion the identification of four new SCA’s (SpinoCere-        predicted from the occurrence of anticipation, they
bellar Ataxia’s): SCA8, SCA10, SCA11 and SCA12.              found an unstable repeat expansion mutation as the
Since then, another two SCA’s have been added:               genetic cause of SCA10. The mutation is of a new type
SCA13 and SCA14. Although perhaps no major break-            and consists of a very large unstable ATTCT pentanu-
troughs have been achieved, progress in understand-          cleotide expansion in one of the gene’s introns. In con-
ing the mechanisms of damage and death of nerve cells        trol persons, the length of this ATTCT ranged from 10-
in dominant ataxia and other neurodegenerative dis-          22 copies, and in patients it was expanded up to sev-
orders is well ongoing. It is the aim of this communica-     eral thousand copies. As with SCA8, this intronic re-
tion to summarize the main achievements in the past          peat expansion is not translated into the gene’s protein
year.                                                        product, but presumably interferes with the gene’s
                                                             transcription. Similar to most CAG repeat expansion
Genetics                                                     disorders, but less pronounced, the length of the pen-
With the number of genetically identified SCA’s still        tanucleotide repeat expansion is inversely correlated
increasing, this year SCA13 and SCA14 have been              with the age at onset.
identified. SCA13 was found in a single French family        Of the known SCA’s, interesting news was reported on
and was reported last July by the group from La Sal-         the genetics of SCA2, SCA7, and SCA8.
petrière in Paris. In this family, affected members          Two sporadic cases of SCA2 from Italy, were shown to
showed slowly progressive cerebellar gait ataxia and         be caused by an abnormal CAT interruption of a nor-
dysarthria with onset in childhood, delayed motor            mal length CAG repeat. This is remarkable, as in
milestones and moderate mental retardation. Some of          SCA1 and SCA3, the age at onset has contrarily been
them also showed signs of spasticity and disturbed eye       related to the uninterrupted CAG expansion. A study
movements (nystagmus), and MRI imaging in two pa-            of a large number of SCA7 families of different ethnic
tients demonstrated moderate cerebellar and pontine          origin showed different haplotypes of the peri-SCA7
atrophy. After exclusion of known SCA mutations and          gene region, indicating different origins or founders. Of
SCA loci in this family, a genome wide search showed         all SCA’s, the instablity of the the CAG repeat expan-
linkage to a new locus on chromosome 19q13.3-q13.4.          sion is highest in SCA7, with a median increase of +6
The gene itself has not yet been identified.                 repeats in paternal transmission and +3 in maternal
One month later, in august 2000, SCA14 was reported          transmission. In line with this, several reports men-
in a three generation Japanese family by the group           tion new mutations from expansion of intermediate
from Sapporo. In this family, progressive ataxia             length CAG repeats. The occurrence of new mutations
started in adult life. Affected people with a relatively     may explain why SCA7, with its strong tendency for
late age at onset (beyond 38 yrs) showed only cerebel-       further expansion in next generations, has not become
lar ataxia, but those with a relatively early onset (be-     extinct.
fore 28 yrs), showed an initial stage with intermittent      The genetics of SCA8 still are somewhat enigmatic,
myoclonus before the manifestation of progressive            because of the occurrence in some countries of ex-
ataxia. Imaging studies in a few members showed              panded CTG repeats in healthy subjects, as reported
cerebellar atrophy without brainstem involvement. A          from Canada, France, the UK, and Finland. However,
genome wide search linked the disorder in this family        reports from other countries as Portugal and Japan,
to a locus on chromosome 19q13.4-qter. It is intriguing      mention no overlap. The clearest separation is seen in
that the SCA13 and SCA14 loci are on the same chro-          Japan with CTG expansions of 89-155 in affected and
mosome 19q, and are actually neighbouring each other         expansions of 15-34 in the population. In Portugal, the
on either side of chr19q13.4. Although clinical mani-        CTG repeat in people with SCA8 ranged from 100-152
festations in the two families obviously differ, the close   copies and in unaffected controls ranged from 15-91,
proximity of their loci suggests the possibility that        with large (40-91 repeats) occurring in less than 1%. In
they might be genetically similar. This reminds of the       Finland, the repeat lenght in people affected with
situation some six years ago, when the gene for SCA3         SCA8 ranged from 100-675, but CTG expansions
was genetically localized in the same region of chromo-      within this range occurred also in 3% of controls, and
some 6p as the gene for Machado Joseph’s disease, but        haplotype analysis pointed to multiple origins.
on clinical grounds was considered to be different, and      Following their original report on SCA8, the group
later the CAG expansion in the MJD gene was also             from Minneapolis confirmed in a further report of the

EURO-ATAXIA                                                                            No. 19 – December 2000

Minnessota kindred that the CTG expansion is directly     shown that in addition to the clinically pure cerebellar
involved in this family. The CTG expansion was longer     syndrome, there may also be pontine atrophy and in-
in affected (mean: 116 CTG repeats) as compared to        volvement of brainstem and peripheral nerves.
unaffected expansion carriers (mean: 90 repeats), with    Further data on SCA7 has come from Belgian and
a pathogenic threshold of 107 repeats. Remarkably,        British studies, which showed a strong correlation be-
very large expansions, beyond 250 repeats, did not        tween the length of the CAG repeat and clinical mani-
cause ataxia. In this family, there was a strong mater-   festations. It appeared that relative mild symptoms
nal penetrance bias, related to expansions in maternal    with onset in adult life occurs with a repeat length of
transmission, and a reduced paternal penetrance, ex-      up to 45 copies, severe disease with adolescence onset
plained by meiotic contractions as demonstrated in        occurred with up to 55 repeats, and childhood onset
sperm. The finding of large CTG repeat contractions in    and rapid fatal course occurred with more than 55 re-
sperm in this family has been confirmed in the reports    peats.
from Portugal and France. The maternal bias seen in       Additional clinical data on SCA8 mention the occur-
this family, was not found in the Finnish study.          rence of spasticity, tremor and sometimes of cognitive
So, the occurrence in the population of large normal      impairment in addition to the prominent ataxia and
CTG repeats in the SCA8 gene shows geographical dif-      variably present spasticity and reduced vibration
ference, and the repeat shows high meiotic (transgen-     sense, as described in the original report. The progres-
erational) instability.                                   sion is relatively slow, and sometimes fluctuations oc-
Among, epidemiological data reported this year, are       Therapy
those from far eastern countries, China, Japan, India     Unfortunately, therapeutic possibilities of the domi-
and Korea, and two European countries, Spain and It-      nant ataxia’s are still minimal.
aly. From previous publications it was clear that         In transgenic SCA1 mice, some transient alleviation of
worldwide MJD/SCA3 is the most prevalent type type        ataxia has been claimed following cerebellar allograft
of ADCA, with the highest percentages of about 80% in     transplantation. In humans with SCA6, some tempo-
Portugal and the Azores. In Spain SCA2 and SCA3           rary improvement was observed in open studies with
have now been found to be the most frequent types,        transcranial magnetic stimulation, and with acetazol-
both accounting for some 15% of all ADCA cases. In        amide, a drug that is also used in episodic ataxia type
Italy a remarkable difference exists between the north    2, one the allelic disorders of SCA6.
and the south. In the south SCA2, the type that is
known for its special occurrence in Cuba and India, is    Etiology
predominant and accounts for about 3/4 of all people      Let me start to summarize what was known or hy-
with ADCA, while in the north SCA1 is the prevalent       pothesized up to last year on the cause of neuronal cell
type, accounting for approximately 2/3 of all people      degeneration in different SCA’s and other disorders,
with ADCA.                                                which are caused by an unstable CAG expansion.
                                                          In SCA1, 2, 3, 7, as in Huntington’s disease, DRPLA,
Clinic                                                    and SBMA (SpinoBulbar Muscular Arophy), the ab-
Studies with electrophysiological measurements have       normally expanded CAG triplet repeat is translated
shown involvement of peripheral nerves in about half      into a polyglutamine aminoacid (polyQ) stretch in the
of SCA1 and SCA3 and about 3/4 of SCA2 patients,          gene’s protein product. In these ‘CAG repeat disor-
and in Cuban SCA2 patients showed a relation be-          ders’, the length of the – unstable – CAG repeat shows
tween the severity of ataxia and central nervous sys-     a strong inverse correlation with the age at onset of
tem conduction slowing, and between loss of reflexes      symptoms, and also with progression of the disease in
and slowing of peripheral reflexes.                       affected persons. With few exceptions, the function in
First recognized to occur in SCA3/MJD, parkinson          the cell of these proteins, named ataxin1, ataxin2,
symptoms which react favourably to levodopa, have         huntingtin and so forth, is not known. In these disor-
now also been described in SCA2. In a study with a        ders, as in all dominantly inherited disorders, both
radiotracer, the occurrence of parkinson symptoms in      normal and abnormal gene products are present. The
SCA3/MJD has been related to a decrease of dopamine       abnormal ataxins with an abnormally large polyQ
receptor sites in deep brain nuclei.                      stretch are called mutant ataxins, and are supposed to
After the report of a second SCA4 family in France        have a harmful gain of function: a function that is
with some additional symptoms to cerebellar and sen-      normally not present.
sory disturbances originally described in the Utah        Among the first findings was an abnormal interaction
kindred, another SCA4 family without sensory distur-      between (mutant) proteins and other proteins, called
bances has now been reported from Japan, possibly         associated proteins (AP). For instance in Huntington’s
further widening the clinical spectrum of this SCA        disease interaction has been found with HAP1, in
type.                                                     SCA1 interaction has been found with LANP (leucine
Imaging and neurophysiological data in SCA6, have         rich nuclear protein), and SCA2 has been found with

No. 19 – December 2000                                                                           EURO-ATAXIA

ataxin-2 binding protein (A2BP1), which is localized in   Using transfected cells in a study on the subcellular
cytoplasmic structures known as the Golgi network.        distribution of ataxin-7, it was found to be bound
Further, in SCA1 was also found that early changes        within the nucleus to the nuclear matrix and the nu-
occurred in gene expression. Soon, it became clear that   cleolus, suggesting that disruption of nuclear matrix,
the polyQ tract in the mutant proteins caused an ab-      or nucleolar function might be involved in the patho-
normal three dimensional folding of the protein, and      genesis of SCA7.
an abnormal tendency to aggregate. The next major         The issue whether NI’s that occur in SCA1, 3, 7, HD,
step was the finding in tissue of both humans and         DRPLA and SBMA are themselves harmful is still de-
transgenic animals with SCA1, 3, 7, HD, DRPLA and         bated. On the one hand it was found that cerebellar
SBMA of small nuclear inclusions (NI’s) in neuronal       Purkinje cells in SCA1 mice, which have defective
cells. In SCA2 and SCA6 abnormal aggregates were          binding to ubiquitin and therefore do not form intra-
not found in the nucleus, but in the cell’s cytoplasm.    nuclear aggregates, have fewer NI’s, but show more
The intranuclear aggregates contained partially bro-      pathology. On the other hand a study in cultured cells
ken down mutant ataxins and also different cellular       with another (non polyQ) aggregating protein, sug-
protein degrading enzymes as ubiquitin and protea-        gested that the presence of intranuclear aggregates is
somes. At first the abnormal aggregates themselves        harmful and causes cell death by nuclear fragmenta-
were suspected to be harmful to the neurons, but in       tion (apoptosis). In a study on the regional expression
HD and SCA1 it was found that prevention of the ab-       of ataxin-7, a strong cytoplasmatic and nuclear expres-
normal protein to aggregate actually enhanced its         sion was found in areas of neurodegeneration, but the
toxic effect, while prevention of the proteins to enter   nuclear expression could not explain all neurodegen-
the nucleus did protect the cells. Thus the NI’s seemed   eration.
to reflect the cell’s defensive handling and partially    The present understanding of neurodegeneration in
succesfull degradation of theses abnormal proteins,       CAG repeat expansion disorders may be summarized
without which they are even more toxic.                   as follows. The abnormal polyglutamine tract in the
In the past year several contributions were made in       mutant protein causes an abnormal folding and by in-
the understanding of various ways of neurodegenera-       teraction or binding to certain cell specific proteins
tion in the spinocerebellar ataxia’s.                     may deplete or functionally hamper other proteins in
From a study with transfected cells, it was found that    their function. The mutant protein may abnormally
when inside the cell’s nucleolus, not only mutant         enter the cell’s nucleolus, where it may undergo an-
ataxin-3 but also normal ataxin-3 adopted a conforma-     other conformational change, exposing the polygluta-
tional change, exposing the polyglutamine stretch.        mine tract. The polyglutamine tract causes abnormal
That the degradation of mutant ataxin indeed is im-       selfaggregation and renders the protein resistent to
paired, was confirmed in a study with SCA1 trangenic      degradation by proteasome enzymes. The presence of
mice. While the first step, in which the mutant ataxin    mutant proteins in the nucleus may cause a stress re-
protein is bound to the enzyme ubiquitin is normal,       sponse with increased levels of protective chaperone
the second step in which the ubiquitin-protein complex    proteins. Within the nucleus, (parts of) mutant protein
is cleaved by proteasome enzymes is disturbed.            may cause altered gene transcription, and further de-
In a SCA1 transgenic mouse it was                         range the cell’s metabolism. As a defensive mecha-
further found that in the Purkinje cells                  nism, intranuclear aggregates may be formed, which
of the cerebellum, several calcium                        contain fragments of mutant protein, protein degrad-
handling proteins (parvalbumin                            ing enzymes as ubiquitin and proteasomes, and a vari-
and calbindin) were reduced                               ety of other more or less cell specific proteins. The
before the appearance of NI’s, and that                   resulting neurodegeneration is related to the length of
these proteins were also included in the NI’s             the polyQ tract, the levels (expression) of mutant
once they appeared. In SCA3 and SBMA, the abnormal        protein, and the duration of the exposure.
NI’s were found to also include CREB Binding Protein      In SCA2, mutant ataxin-2 remains localized in the cy-
(CBP). CBP is a protein, which activates DNA tran-        toplasm, and cells in regions of neurodegeneration
scription, and enhanced levels of this protein protect    show cytoplasmic microaggregates without ubiquitin.
cells against toxicity of proteins with a polyglutamine   However, with special labeling technique, ubiquinated
tract.                                                    intranuclear aggregates have now been demonstrated
In SCA3 transgenic fruitflies the NI’s were found to      in cells other than the cerebellar cells, which are most
also include certain heatshock proteins (Hsp’s). Hsp’s    at risk.
belong to the group of chaperone proteins, which serve
to protect proteins against damage. In SCA3 trans-        The mechanisms of neurodegeneration in SCA6, SCA8,
fected cells, increased levels of a certain Hsp chaper-   SCA10 and SCA12 differ from that caused by polyglu-
one protein suppress polyglutamine protein aggrega-       tamine toxicity.
tion, but increased levels of another Hsp (Hsp70) may     In SCA6 a small and relatively stable CAG expansion
also protect the cell against toxicity of polyglutamine   causes a change in a protein subunit of a calcium
proteins.                                                 channel that is preferentially expressed in Purkinje

EURO-ATAXIA                                                                                  No. 19 – December 2000

cells. In these Purkinje cells, small rod-shaped cyto-         genes overlap, influencing each others transcription.
plasmic aggregations have been identified, which con-          This neighbouring gene codes for a cytoskeleton pro-
tain calciumchannel proteins, but which are not                tein in brain cells.
ubiquinated.                                                   The mutation of SCA10 exists of a very large intronic
Study of the mutant calcium channnels expressed in             pentanucleotide. How this affects the transcription or
cells have now showed altered channel characteristics          perhaps the gene product is not yet clear.
of opening and closing, which suggest the possibility of       As mentioned in last year’s update, the CAG repeat
excessive calcium entering into the cell. Calcium over-        expansion in SCA12 is remarkable for its localization
load in the cell may cause a metabolic disturbance and         in the gene’s promotor site. This mutation is suggested
an impairment of mitochondrial function, which in              to cause an excessive amount of the gene’s product,
turn may lead to energy failure and cell death. From           which is otherwise normal. The SCA12 protein plays a
these data it appears that SCA6 can be considered to           steering role for an enzyme, indicated as PP2A or
be a ‘channelopathy’, similar to Episodic Ataxia type 2        PPP2R2B, which is involved in processes of aging and
(EA2).                                                         death of certain brain cells, posssibly explaining the
In SCA8, the genetic mutation consists of an unstable          neurodegeneration in SCA12.
CTG trinucleotide expansion in an untranslated part
of the DNA, which often shows an expansion in mater-           Summary
nal transmission and a contraction in paternal trans-          This year has welcomed two new SCA’s and the clon-
mission. As the protein product of the gene is not ab-         ing of one gene. New genetic and clinical data have
normal, it was not at first clear how this untranslated        been reported on SCA6, 7 and 8, and insight in polyQ
trinucleotide expansion might cause a gain of function,        toxicity has further deepened, but therapeutic possi-
as is suggested for the CAG repeat expansions. While           bilities have not yet been realized.
the genetics of SCA8 still aren’t completely clear, and        While research on these disorders is gradually but
a CTG expansion not always leads to SCA8, the Min-             steadily moving forward, hopefully leading to better
neapolis group has now found that the transcription of         possibilities of treatment in the future, let’s not forget
the last part of the SCA8 gene is performed via the            to experience life as it comes this day, and to be invol-
first part of the neighbouring gene, and that these two        ved as much as we can.

SCA                 MIM                  Chromosome           Repeat              ADCA                 OPCA

SCA1                164400               6p22-23              CAG                 I                    I, IV
SCA2                183090               12q23-24             CAG                 I                    I
SCA3/MJD            109150               14q32.1              CAG                 I                    ‘Azorean’
SCA4                600223               16q24-ter            ?                   I/III
SCA5                600224               11c                  ?                   III/I
SCA6*)              183086               19p13                CAG                 III ‘Holmes’
SCA7                164500               3p14-21              CAG                 II                   III
SCA8                603680               13q21                CTG                 I                    (I/VI)
SCA10               603516               22q13-ter            ATTCT               III/I
SCA11               (n.a.)               15q14-21.3           ?                   III                  -
SCA12               604326               5q31-33              CAG                 (I)                  -
SCA13               ?                    19q13.3-13.4         ?                   I
SCA14               ?                    19q13.4-ter          ?                   III

DRPLA               125370               12p                  CAG                 -                    ‘Haw River’

EA1                 160120               12p                  KCNA1, potassium channel, mutation
EA2*)               601011               19p13                CACNA1A, calcium-channel, mutation

*) allelic disorders: different mutations in the same CACNA1A calcium channel unit gene.

Table 1. Genetically identified dominantly inherited ataxia’s, comparing SCA numbers, Mendelian Inheritance in Man
(MIM) numbers, the chromosomal localization of the gene, the mutation, and their comparative ADCA/OPCA classifica-

No. 19 – December 2000                                                                                EURO-ATAXIA

‘BILOXI BLUES’                                                tant result the upcoming trial with Idebenone and
                                                              CQ10 at the end of this year.
Jon Bunnig                                                    A good innovation was the opportunity to have your
                                                              lunch together with a scientist/neurologist. I was not

I n Europe, it’s sometimes very difficult to whip up
  sufficient enthusiasm among ataxic people to or-
ganise an Ataxia weekend. I experienced this myself a
                                                              there, but I heard it was very successful. Knowing that
                                                              most of the scientist do not see any more than micro-
                                                              scopes and laboratories for them it is also nice to meet
few months ago in Holland. But in America it is com-          the people behind the DNA.
pletely different: in the country were everything is big,
bigger and biggest, people from all over the continent        To do research for FA a lot of DNA material is needed.
and beyond come together to attend a conference about         During the conference it was possible to give blood
ataxia for three days. This year, more than 400 people        samples for research. I was amazed by the many vol-
– ataxians and their relatives – came together in             unteers and afterwards I feel sorry that I was too
Biloxi, Mississippi between 24 and 26 March; and I            afraid for a needle to donate.
was one of them.
                                                              Also the finishing gala dinner was like you may expect
The conference was organised by the National Ataxia           of the Americans: very big, including tom bola and per-
Foundation and this year the main issue was the new           formances of some local artists. But again, due to the
millennium; a new millennium in which, keeping the            amount of people and the noise, it was difficult to have
current scientific research in mind, a treatment or           some relaxing discussions. Soon after the dinner some
even cure for FA might be reasonably expected in the          people escaped to a bar at the 32nd floor to enjoy the
near future. Maybe a few people came to Biloxi to hear        beautiful view at the Gulf Coast. A very nice evening
where they were hoping to hear, but for most people it        were a lot of addresses and phone numbers were ex-
was the opportunity to see old friends and meet new           changed.
ones. It was a social occasion as much as a scientific
one.                                                          After the conference I stayed in America for a couple of
That the social aspect would be very important was            nights. In America it is possible to rent a adapted car
soon clear at my arrival: the conference was located in       and I wanted to visit New Orleans. In contrary with
an extremely large hotel with 32 (!) floors and 3 ca-         other big cities in America, New Orleans is not very
sino’s. I am still not sure if it was a hotel with a casino   suitable for people in wheelchairs. Very pity, especially
or a casino with bedrooms, but at least they had              because it is a very nice town. The sun was very hot
enough fully accessible rooms and that is what counts.        and after getting the wheelchair in and out of the car
A disadvantage of such a large hotel is of course the         several times to find a reasonable priced hotel I de-
long distances to get to where you want to go to. For         cided to return to Mississippi to spent some days at
most journeys the shortest way was going through the          the coast. For people from Europe it is so amazing that
casino. But this was noisy, and if you know that a lot        almost every hotel has at least one adapted room and
of ataxians get irritated by background noises, I think       in bars and restaurants you certainly will find an
this hotel was maybe not the best choice. Fortunately         adapted bathroom, so great!
it does not irritate me that much and I also like to
gamble a little, but after three days of non-stop casino-     Next year the conference will be in Michigan. In that
sound, I was happy to find some silence outside the ho-       period it is freezing there, so I will not attend. But as
tel.                                                          soon it is in a warmer place, I certainly will try to be
I had already arrived in Biloxi a few days before the         there again.
actual starting of the conference. Sitting at the en-
trance of the hotel enjoying the Mississippi sun, I was
surprised by so many ataxians entering the building:          ‘DRUNK AS A SKUNK’
people using wheelchairs, crutches or each other from
all over the country, it was very impressive! This year       Lieuwe Koopmans
people even attended from Brazil, Japan, Germany,
Scotland, England and The Netherlands. A lot of dif-
ferent people, being in different stages of their illness,
but having something in common. Soon I met other
                                                              T   hose who are acquainted with FA know that the
                                                                  disease begins with a period of slightly unstable
                                                              walking. The outsider often draws the conclusion that
ataxians and we had very interesting discussions              the affected person is drunk. When the affected person
about the differences in how people experience FA in          starts to use a wheelchair, people think differently.
Europe and America.                                           Then a person is really disabled.
The guests who were invited to speak at the conference        When Erik started to study at one of the universities
all had a clear story, but did not bring any news. It         in Holland he joined a student association. Of course
had to be clear for all different listeners, so most of the   the unstable gait of Erik was certainly noticed by the
discussions were very general. I found the most impor-        association’s staff and in communication with Erik it

EURO-ATAXIA                                                                                 No. 19 – December 2000

was decided that he wouldn’t participate in all events        MORE THAN JUST MEDICAL
during the introduction. (He couldn’t win at sport
games, but he scored well at quizzes and other activi-        Michael Morgan
ties requiring prowess. When you spend your time do-
ing sports, visiting disco’s, etc., you don’t have time for
reading books. So thank heaven Erik has always liked
reading books.)
                                                              A    lthough there didn’t seem much in the way of con-
                                                                   troversy at last year’s Euro-Ataxia AGM Jon Bun-
                                                              nig’s intervention during the endless series of medical
One of the mandatory activities of student life is vis-       and scientific analyses was significant I felt. Jon
iting pubs. Erik wasn’t released of that job. He already      seemed to get annoyed at the medical peoples’ contin-
knew that alcohol could have a fatal effect on his            ual use of the term ‘patient’ in their explicitly clinical
walking, also his driving. So on the evening this par-        discussions. “I am not a patient,” fumed Jon in re-
ticular tale took place Erik didn’t drink at all.             sponse (although he forgot to add ‘I am a free man’
                                                              which would have had a nice ring). Jon’s intervention
It was already getting late when he and his fellow stu-       raises issues which are both topical and challenging –
dents visited the pub of this story. The students             topical because of the new thinking on disability and
quickly took their seats on the barstools and ordered         how it is seen, and challenging because of its direct
drinks. But the bartender who took the order had al-          questioning of medical assumptions regarding ataxic
ready noticed Erik’s unstable gait as he walked in and        people.
had drawn his own conclusions, for when he came to
Erik he said in a disapproving tone: “You won’t get a         To the medical profession ataxic people are simply
drink, you’re already as drunk as a skunk!”                   people who present the clinical manifestations of
                                                              ataxia. To ataxic people they are this but yet are so
Several years later Erik and a friend were on holiday         much more than this. This may sound puzzling, even
in Ireland. Erik was already using a wheelchair. With         Hegelian, so let me try to explain. To the clinicians
the help of the Irish organisation for muscular dis-          with whom the ataxic person interacts he or she is a
eases they had found some guesthouses that had been           ‘patient’ – a passive recipient of care – and we can
made accessible to disabled visitors through the addi-        agree that it is legitimate to be referred to as ‘patient’
tion of a few adaptations. Alas, the road over the hill       within a medical context. After all one attends a hospi-
from the guesthouse to the local pub wasn’t at all ac-        tal if one is sick, in the same way that one attends a
cessible, and Erik’s friend/helper had to push Erik’s         dentist if a tooth hurts. At this level its merely a ques-
wheelchair uphill for more than a kilometre. Out of           tion of terminology nothing more. But the problem
breath and exhausted he sank down on the first chair          arises when the same terminology is used outside the
in the pub. The regular guests were astonished and            medical context. We can refer to this as medicalisation
curious about the two English-speaking foreigners, one        – seeing all aspects of life from within a medical frame
of them sitting in a wheelchair. Irish people are known       of reference even when the problems that the person
to be curious, generous and fond of talking – especially      might be facing may have more to do with the social
when they’re in the pub. They began to ask Erik all           (or personal) than the medical side of things. For the
sorts of questions – where he came from, why he was           ataxic person does not simply exist within a clinical
in a wheelchair, if he still had a job, what way he had       setting alone. He or she is also a definite historical
travelled, and so on. His answers, spoken correctly but       being and exists in many other dimensions apart from
in a distinctly foreign accent, were very much appreci-       the clinical one. He or she has a social background,
ated. Every question was accompanied by the gift of ‘a        and a personal background, and an educational back-
drop of whiskey’. After he had drunk the first two            ground, and also a sexual background. The ataxic per-
glasses sip by sip, there were already a queue of drinks      son will not so much be focused on the merely physical
on the table waiting to be drunk. But nothing was of-         aspects of the disease but crucially how these disabili-
fered to his hot, sweaty and now exhausted friend, not        ties work through into his or her opportunities in life
even a drop of beer – although one could easily see           and most central of all on his or her conception of self.
that he was very thirsty, having pushed Erik all the          In sum, what is paramount to the ataxic person is not
way uphill. Alas, his friend had to buy his own glasses       ataxia itself but living with ataxia.
of beer and after his extreme thirst was quenched, he
started helping Erik to empty the queue of ‘drops of          Coming back to Jon’s intervention then, it may be ap-
whiskey’ that covered the table-top.                          propriate to speak of ‘patients’ within a medical con-
Nevertheless, two remarkable histories that illustrate        text but certainly not within the wider social and per-
the surprising effects of a wheelchair.                       sonal context wherein ataxic people live. This I think
                                                              is what infuriated Jon in Westende. Alas the clinicians
                                                              and scientists present didn’t seem to have any aware-
                                                              ness of this difference in perspective between them-
                                                              selves and ataxic people, that what they saw and dealt
                                                              with in the clinic was a partial and even lesser reality

No. 19 – December 2000                                                                               EURO-ATAXIA

to most ataxic people. The whole idea behind the            father drove me to school before he went to his office.
Westende conference was to afford clinicians, scien-        He always brought me to the front entrance while the
tists some kind of insight into how life is lived by        other pupils went inside through the back door. Before
ataxic people. But, as we know now, there was little        I reached the wardrobe a wide corridor had to be
opportunity for interaction and so no genuine insight       crossed. It took me quite some concentration to cross
was gained.                                                 that corridor without collapsing and falling to the
                                                            floor. One morning the concierge offered me his arm to
In conclusion, the reason why many ataxic people –          lean on. I refused. I wanted nobody’s help. But having
like Jon – get angry at being called ‘patients’, is be-     crossed halve of the corridor I couldn’t keep myself
cause it suggests that the ataxic person is not a person    upward anymore and collapsed. I felt so ashamed!
in his or her own right and does not have to be re-         Falling down was humiliating already but this was
spected as such, but is simply a medical phenomenon,        even worse: trying to save my pride but failing so
a collection of syndromes. Which we are, but we are         demonstratively. The concierge helped me up again
also much more than that                                    and accompanied me to the wardrobe. The next
                                                            morning the concierge again offered me his arm to lean
                                                            on and this time I was wise enough not to refuse. From
ACCEPTING HELP                                              that day onward he helped me every morning.
                                                            By chance one of my classmates saw the concierge help
Carolien Koopmans                                           me. I don’t know if it was an agreement between my
                                                            classmates but the switching of classrooms became a

O     ne of the most difficult problems of FA – and
      probably of all ataxias – is having to accept help.
At onset the symptoms are so light that you can easily
                                                            lot easier for me since that day. Every time we had to
                                                            move to another classroom one of my classmates took
                                                            my bag and another one offered me his or her arm to
go on doing everything on your own. But inevitably          lean on. Moving through the building almost became a
there comes a time when some assistance is needed.          leisure. Even more important was that I began to relax
Since I’m in a wheelchair for more than 25 years, I am      psychologically too. Not having to concentrate totally
able to look back on my career as FA’er with some dis-      on my movements there was time left for some small-
tance. Let me tell you about my experiences with the        talk. Encouraged by my more relaxed attitude my
acceptance of another person’s help.                        classmates began to feel more at their ease in my com-
The most problematic stage of FA is for the bulk of ‘pa-    pany too. I realised that my classmates were a lot nicer
tients’ and parents the period that begins with a           than I had always supposed.
slightly disturbed gait and ends with walking like a        That experience made me think a lot about my sense
drunk. At the end of this stage a wheelchair surely         of self and self-esteem, pride and the question of ac-
comes into sight. I went through that awful stage           cepting help. Was it as wise as I had simply believed it
when I was in secondary school, at the age of 12 to         was to refuse every offer of help? Did my sense of self
nearly 18. The secondary school I attended was an old       really forbid me to accept any well meant assistance,
building with wide corridors and stairs. When I was in      even if I couldn’t do without? And if it did, wasn’t there
first grade I had little or no problems finding my way      something wrong with my sense of pride? Didn't that
through the building. But every year it became more         arrogant attitude of mine stand in the way of much
difficult to walk up and down the stairs and cross the      human warmth that I might otherwise encounter?
corridors. And every year having to stand all those         Was I really worth less now that I sometimes needed
new pupils gazing at me as if I was a kind of circus at-    someone to lean on when I walked. Anyway I felt much
traction. I had to change classrooms every hour. After      more at ease now that I accepted help. And was my
a few years I was so busy with dragging myself              sense of physical independence more important than
through school that it didn’t cross my mind to ask for      my psychological health?
help. And maybe I was inspired by some sense of pride.      Nowadays I need assistance with a lot of things. I am
That sense of pride is very understandable when             glad to have learned to receive help in such a relaxed
something weird is happening to your body and you           way. And I am proud of being able to live my life and
yourself haven’t got the faintest idea what is happen-      communicate with other people in such a normal way.
ing. In my case the GP and neurologist preferred not to
inform my parents and me, but I doubt if it would have
made any difference if they had told what was hap-          THE GIFT
pening; I might have understood it rationally but I
wouldn't have understood it emotionally.                    Michael Morgan
When I was beginning my 6th and final year at secon-
dary school my mother forbade me to ride on my bicy-
cle any longer. (Looking back now I must confess it
was a right decision of her, but at that moment I
                                                            C   oming soon to a video screen near you, a play cen-
                                                                tred on FA. Plans are underway to produce Euro-
                                                            versions of ‘The Gift’, translating it from its original
wasn’t pleased at all!) However, in the mornings my         English into Spanish. German, French, Italian and

EURO-ATAXIA                                                                                  No. 19 – December 2000

Dutch copies. The Gift is a play trying to convince the       almost 300 people who subscribed as friends, support-
public on the benefits of pre-natal genetic testing – to      ers, promoters and sponsors – after not even one year
“raise awareness of genetic selection and the ethical         of activity!
implications it could play on peoples lives,” as it’s pro-    Switzerland is a small country with big problems of
ducers UK Welcome Trust put it.                               language and mentality. All of us, aCHaf, FA-CH (and
                                                              soon we might have to look for an Italian name!)
It’s probably the first cinematic treatment of FA but I       strongly favours treatment of FA with Idebenone. In-
wasn’t oversold by it. In particular I found the charac-      ternational research in this area is followed with much
terisation of ‘Annie’, the girl with FA, disturbing. In       interest. Orientation is, in this respect, with the
one scene she was portrayed huddled in a corner               French Friedreich's Ataxia group (AFAF) and its
whining such lines as: “My life is over, there's no hope      medical board. Our main goal is to have Idebenone
for me,” etc., etc. I certainly felt like giving her a good   registered as quickly as possible in the official Swiss
kick up the backside and telling her to get on with life.     health system. So far, we have succeeded in importing
Life with FA might be more difficult than most, but it        a large stock of Idebenone from Italy, and the medica-
can still be lived well.                                      tion can be obtained for a reasonable price. Private
                                                              sponsors were found to give our members financial
FA was probably deliberately selected in ‘The Gift’ as a      support and we are in continual contact with the Swiss
genetic disease of choice, meaning that it filled the         branch of the Japanese manufacturer Takeda.
dramatic requirements of being wholly negative,               On the political side letters are being written to Fed-
blacker than black, providing excellent scope for an          eral Councils, and dialogues are being held with key
exploration of issues surrounding genetic testing and         persons in the bureaucratic system (aurgh!). We ap-
termination. But the criticism that this was a one-           pear on TV and in newspapers so that people might
dimensional view of FA went unheard. FA is not sim-           gain awareness of what ataxia is and so become sensi-
ply an unmitigated disaster, so inherently terrible a         tive to our needs.
fate that it must be avoided at all costs. The truth of       Which is most important: to concentrate on the medi-
FA is, rather, multi-dimensional. Impairment is but           cal side alone or to bring in social and personal mat-
one dimension. There are others – personality, educa-         ters? Our primary medical task might be to inform our
tion, etc. Within these limits people with FA do indeed       members on research in general, and on Idebenone in
lead rich and meaningful lives – a point which Euro-          particular. But then, we live a private life, too. We try
Ataxia should always be keen to promote. But the play         to establish an atmosphere of friendship and confi-
was really about the uses and implications of pre-natal       dence between our members and we try to open access
genetic testing. FA was used more as illustration of          to the world.
this than as being the play's subject.                        We are still very very young, lacking experience and –
                                                              money… So it will take time to bring all our projects
Pre-natal genetic testing and termination of diseased         into reality.
foetuses is an entirely legitimate course of action for       Our web-site: was created in French. It
prospective parents caught in this cruellest of dilem-        is, at the moment, being translated into German and
mas. But as far as my and many other ataxic people's          English. Give us the pleasure of your visit!
involvement goes it's never more than second best. We
are motivated by the possibility of treatment, maybe          S. Zollinger, president
even ‘cure’, not prevention through genetic testing and       D. Iser (FA), vice-president
termination. Maybe Euro-Ataxia and a few other or-            A. Matthey, secretary
ganisations should start being a little more critical to-     N. Riemann (FA), treasurer
wards the output of the genetics establishment, such
as the Welcome Trust and remember that there is               Association suisse de l’Ataxie de Friedreich (aCHaf)
more to life with FA than a mutation on the DNA               La Chenaletta
molecule.                                                     CH-1566 St-Aubin
                                                              Tel: +41 26 6772256
                                                              Friedreich Ataxie-Gesellschaft Schweiz (FA-CH)

T   he Swiss Ataxia Association…
    … was founded in October 1999 in the French
speaking part of Switzerland by Sabine Zollinger, the
                                                              Rütihofstrasse 51
                                                              CH-8049 Zürich
                                                              Tel: +41 1 3402323
mother of two girls with FA, and some friends. A few          Fax: +41 1 3402324
months later, a branch in the German speaking part of         E-mail:
the country is on its way.
In September 2000, there are 43 members with FA or
with some other ataxia in the Swiss Association, and

No. 19 – December 2000                                                                                             EURO-ATAXIA

EURO-ATAXIA BOARD                           EURO-ATAXIA MEMBERS                           Schweizerische Gesellschaft für
Ewout Brunt, President                      Association Belge de l’Ataxie de Friedreich   Friedreich Ataxie-Gesellschaft Schweiz
Hooiweg 72                                  Rue Longue 68                                 c/o Daniela Iser
NL-9761 GT Eelde                            B-6260 Bouffioulx                             Rütihofstrasse 51
NETHERLANDS                                 BELGIUM                                       CH-8049 Zürich
Tel/Fax: +31 50 3091109                     Tel: +32 71 504248                            SWITZERLAND
E-mail:              Deutsche Heredo-Ataxie Gesellschaft e.V.      Tel: +41 1 3402323
Michel Koenig, Vice-President               Haussmannstrasse 6                            Fax: +41 1 3402324
IGBMC                                       D-70188 Stuttgart                             E-mail:
1 rue Laurent Fries, BP 163                 GERMANY
F-67404 Illkirch Cedex-C.U. de Strasbourg   Tel: +49 711 2155114                          CONTACTS IN EUROPE
FRANCE                                      Fax: +49 711 2155119                          Ataxia Telangiectasia Society
Tel: +33 3 88653399                         E-mail:                        33 Tuffnells Way
Fax: +33 3 88653416                         Associazione Italiana per la lotta alle       Harpenden
E-mail:          Sindromi Atassiche                            Herts AL5 3HA
Dagmar Kroebel, Secretary-General           Viale S.Lorenzo-Residence ‘Azalea’ 12/E 2     UNITED KINGDOM
Haagwindelaan 19                            I-00040 Tor S.Lorenzo-Ardea (Roma)            Tel: +44 1582 761437
B-3090 Overijse                             ITALY                                         Fax: +44 1582 765014
BELGIUM                                     Tel: +39 6 91014662                           Friedreich’s Ataxia Society of Ireland
Tel: +32 2 6571510                          E-mail:          San Martino
Fax: +32 2 6576176                          Friedreich’s Ataxia Group                     11 Mart Lane
E-mail:            10 Winchester House                           Foxrock
Theo Schimmel, Treasurer                    Kennington Park                               IRL-Dublin 18
Roggeveld 41                                Cranmer Road                                  IRELAND.
NL-3764 ZC Soest                            London SW9 6EJ                                Tel/Fax: +353 1 2894788
NETHERLANDS                                 UNITED KINGDOM                                E-mail:
Tel: +31 35 6019382                         Tel: +44 20 7582 1444
E-mail:                 Fax: +44 20 7582 9444                         CONTACTS OUTSIDE EUROPE
Evelyne Delion                              E-mail:                  National Ataxia Foundation
3, allée Xavier Bichat                      Asociacion Madrilena de Ataxias               2600 Fernbrook Ln
F-77420 Champs/Marne                        Hereditarias                                  Suite 119
FRANCE                                      C/. Galileo 69, 1º                            Minneapolis, MN 55447
Tel/Fax: +33 1 64687036                     E-28015 Madrid                                USA
E-mail:           SPAIN                                         Tel: +1 763 5530020
Peter Reussner                              Tel: +34 1 4482169                            Fax: +1 763 5530167
Hinrich-Thiess-Strasse 52f                  VSN – Werkgroep Ataxie van Friedreich         E-mail:
D-22844 Norderstedt                         Haagweg 306                                   Association Canadienne de L’Ataxie de
GERMANY                                     NL-2324 NC Leiden                             Friedreich
Tel/Fax: +49 40 55446898                    NETHERLANDS                                   3800, Rue Radisson, Suite 11
Marco Meinders                              Tel: +31 71 5320660                           Montréal, Québec H1M 1X6
Antilopespoor 482                           E-mail:                         CANADA
NL-3607 VP Maarssen                         ADCA-Vereniging Nederland                     Tel: +1 514 8991586
NETHERLANDS                                 Fazantenkamp 839                              Friedreich’s Ataxia Association of New South
Tel/Fax: +31 346 580417                     NL-3607 EC Maarssen                           Wales
E-mail:                       NETHERLANDS                                   31a Chisholm Street
Eila Niemi                                  Tel: +31 346 563913                           Turramurra, 2074
Box 15, Seppäläntie 90                      E-mail:                         Australia
FIN-21250 Masku                             Suomen MS-Liitto – Finlands MS-Förbund        Tel: +61 2 94408233
FINLAND                                     Rare Neurological Disabilities Group          E-mail:
Tel: +358 2 4392130                         Box 15, Seppäläntie 90
Fax: +358 2 4392133                         FIN-21250 Masku
E-mail:             FINLAND
Manuela Bruscia                             Tel: +358 2 4392111
Via delle Badie 39                          Fax: +358 2 4392133
I-50047 Prato                               E-mail:
ITALY                                       Connaître les Syndromes Cérébelleux
Tel: +39 0574 631393                        3, allée Xavier Bichat
E-mail:                   F-77420 Champs/Marne
Michael Morgan, Editor Euro-Ataxia          FRANCE
2 Glenhill Park                             Tel/Fax: +33 1 64687036
Glen Road                                   E-mail:
Belfast BT11 8GB                            Ataxia Group – Neurologiskt Handikappades
NORTHERN IRELAND                            Riksförbund
Tel: +44 2890 302944                        Box 3284
Fax: +44 2890 302973                        S-10365 Stockholm
E-mail:      SWEDEN
                                            Tel: +46 8 6777010
                                            Fax: +46 8 241315

          Euro-Ataxia is registered as a charity in Belgium: VZW 9240/92
          Secretary-General: Dagmar Kroebel, Haagwindelaan 19, B-3090 Overijse, Belgium
          Tel: +32 2 657 1510; Fax: +32 2 657 6176; E-mail:; WWW:
          Bank: Dexia, Pachecolaan 44, B-1000 Brussels; acc. no. 068-2063656-08

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