Rett News Summer 2013

SUMMER 2013 EDITION
RS News
Rett Syndrome Association Scotland
“David & Victoria setting off at the start of the
Coast to Coast Relay for Rett 2013”
In this issue:
Mark Bailey Report • RS Europe • Music Therapy Booklet
Badaguish • Roadshow • Relay Report
Eurordis • Accounts • AGM • Future Events
Fish Oil
Dr Jane McKenzie, Senior Lecturer in Biochemistry and Metabolism and Programme
Leader for BSc Human Biology, Queen Margaret University College, Musselburgh
Back in February a member contacted the Association
with a query about the use of Norwegian Fish Oil,
which she hoped would be of benefit to her Rett
daughter.
Unfortunately the cost of the oil was high - £31 per
bottle and she wondered if there was anything else
suitable but cheaper.
At about the same time an article appeared in the
Herald newspaper regarding a programme set up to
test the amount of Omega-3 fatty acids a family
would consume over a six week period, the aim being
to improve the nations’ health by encouraging people
to include more Omega-3 in their diets. This programme
had been designed by expert nutritionists at Queen
Margaret University College in Musselburgh.
Dr Jane MacKenzie, Senior Lecturer in Biochemistry
and Metabolism and Programme Leader for BSc
Human Biology at the University was contacted and
she has very kindly provided us with the following
information:“The evidence for a potential benefit of long-chain omega-3
fatty acids (often referred to as EPA and DHA found in Fish
Oil) in Rett Syndrome is currently very scarce, but could
be promising. I believe that the most recent paper,
which can hopefully be accessed through this link
www.ncbi.nlm.nih.gov/pmc/articles/PMC3380188/,
does
indicate potential benefits from taking very large doses of
fish oil, however only a very small number of participants
were involved and the study has not been repeated as yet.
My opinion is therefore that the benefits of fish oils in reducing
the symptoms of Rett Syndrome need to be confirmed with
further research before we are able to recommend the use of
fish oil or indeed the appropriate dose to use.
The fish oil supplement used in this research is Norwegian
and likely the one that was mentioned at a cost of £31 per
bottle, which is indeed very expensive. The active ingredients
of any fish oil (the EPA and DHA) are equivalent regardless of
where they are produced, although there are differences in
the amount of these fatty acids provided by commercially
available products. Therefore, I do not believe that there is
any reason to use the specific fish oil used in this study,
particularly as it is sold at a premium price! However, if your
members feel that they want to provide their child with fish
oils based on the existing evidence, then there is no reason
not to, but I would suggest that they purchase a cheaper fish
oil product – as we do not know what might be an appropriate
dose, I would suggest a ‘high EPA/DHA’ product providing
around 450mg (DHA+EPA) per day which is the recommended
dietary dose to gain some health benefits related to
maintenance of eye and brain function and reducing the risk
of heart disease.”
Dr McKenzie has also sent the following article for our
information:-
IMPROVING OMEGA-3 INTAKES OF
PRESCHOOL CHILDREN IN THE UK
Dr Jane McKenzie PhD RD, Senior Lecturer in Biochemistry
and Metabolism, Queen Margaret University, Edinburgh,
Scotland.
The benefits of long chain omega-3 fatty acids (LC n-3 PUFA)
in childhood are extensively documented. Not only do they
play a key role in optimizing cognitive, behavioural and
visual development(1), but they also provide protection
against the development of cardiovascular disease(2). Breast
milk provides a reliable source of LC n-3 PUFA during infant
development and the majority of infant formulas are
supplemented with these fatty acids in an attempt to mimic
the composition of breast milk and offer the same benefits.
However, as a child is weaned, there is increased reliance on
dietary sources of LC n-3 PUFA.
Oily fish provide the only significant source of naturally
occurring LC n-3 PUFA in our diet. According to the 2009
National Diet and Nutrition Survey(3), however, the average
intake of oily fish in children aged 3-5 years of age is just
24.5g per week, and this is primarily attributed to the
relatively few children consuming oily fish on a regular basis.
So why are intakes of oily fish so low in this population?
Unfortunately, many negative preconceptions exist which
appear to inhibit the incorporation of oily fish into children’s
diets. Aside from the apparent strong taste and smell(4), oily
fish is considered expensive as there is a lack of confidence
about how to prepare and serve it(5). In addition, despite
assurances to the contrary, oily fish are often associated with
the ingestion of pollutants which may put health at risk(6).
These influences are particularly pertinent for children growing
up in areas of deprivation, where eating habits are already
suboptimal and resistant to healthy eating messages(7).
Preschool provides a suitable environment for introducing
and reinforcing positive eating habits. In particular, the
immediacy of developmental needs for LC n-3 PUFA would
suggest that this is the ideal opportunity to influence
preferences for oily fish. An initiative was therefore set up to
develop and evaluate a range of omega-3 rich snack foods,
containing oily fish, provided to children attending a
nursery in a deprived area of Scotland(8). Acceptability and
subsequent consumption of the omega-3 rich snacks was
comparable to that of the regular snacks, yet provided a
valuable 250mg more LC n-3 PUFA per portion.
These findings indicate that oily fish can be successfully
introduced into the diet of preschool children and that
such an initiative can contribute to achieving current
recommendations for LC n-3 PUFA intake.
[1] Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A.
Significance of long-chain polyunsaturated fatty acids
(PUFAs) for the development and behaviour of children.
Eur J Pediatr 2010;169:149-64
[2] Adkins Y, Kelley DS. Mechanisms underlying the
cardioprotective effects of omega-3 polyunsaturated fatty
acids. J Nutr Biochem 2010;Apr 9 [Epub ahead of print]
[3] National Diet and Nutrition Survey. Headline results
from year 1 of the rolling programme. London: Food
Standards Agency. Accessed online:
www.food.gov.uk/science/dietarysurveys/
ndnsdocuments/ndns0809year1 (June 22nd 2010)
[4] Sioen I, Huybrechts I, Verbevcke W, Van Camp J,
De Henauw S. n-6 and n-3 PUFA intakes in pre-school
children in flanders, Belgium. Br J Nutr 2007;98:819-25
[5] McManus A, Burns SK, Howat PA, Cooper L, Fielder
L. Factors influencing the consumption of seafood among
young children in Perth: a qualitative study. BMC Public
Health 2007;7:1-7
[6] Freire C, Ramos R, Lopez-Espinosa M-J, Diez S, Vioque J,
Ballister F, Fernández M-F. Hair mercury levels, fish
consumption and cognitive development in preschool
children from Granada, Spain. Environmental Research
2010;110:96-104
[7] Craig LCA, McNeill G, MacDiarmid JI, Masson LF, Homes
BA. Dietary patterns of school-age children in Scotland:
association with socio-economic indicators, physical activity
and obesity. Br J Nutr 2010;103:319-34
[8] McKenzie J, Scheers Andersson E, Drummond S.
The evaluation of an initiative to provide omega-3 rich
snacks to preschool children in a deprived area of
Edinburgh. Presented at the Scottish Lipid Discussion Group
Meeting, Stirling, June 2010
Also, an item appeared in the minutes of the General
Assembly of Rett Syndrome Europe, London, 17th November
2012 as follows:-
FISH OIL
RSE has been approached by the Norwegian Fish Oil
Company to promote their product. They say that their
product is very pure. The company has made extravagant
claims about the benefits of their fish oil. They say that the
membrane in red blood cells is abnormal.
The product has been given to young girls and therefore it is
difficult to see if the improvement is developmental or as a
result of taking fish oil. It would need to be followed up
scientifically. A trial costs a lot of money, for instance the
clinical trial in France about desipramine for 36 people with
RS costs about 500,000¤ . It is debatable if there is enough
evidence to conduct a trial.”
Research Update
by Dr Mark E. S. Bailey (School of Life Sciences)
& Dr Stuart R. Cobb (Institute of Neuroscience and Psychology)
College of Medical, Veterinary and Life Sciences, University of Glasgow
RSAS has awarded £7,000 to Dr Bailey and Dr Cobb for a
project over 2 years entitled “Is protein therapy a viable
strategy in Rett syndrome?”.
The rationale for this project stems from the work already
completed in Dr Bailey and Dr Cobb’s laboratories with the
support of RSAS. It has been demonstrated that there is an
ongoing requirement in brain cells for the MeCP2 protein
beyond early development and throughout adult life.
It is also clear that if MeCP2 can be provided to the cells of
mice lacking the Mecp2 gene (a good genetic model for Rett
syndrome), the cells can begin to function normally and the
condition of the mouse itself can improve markedly. As Dr
Cobb and Prof Bird showed in 2007, this can be achieved in
Mecp2 knockout mice by reactivating the gene.
This will not work in human RTT patients, however. Dr Bailey
and Dr Cobb have more recently shown that supplying the
MECP2 gene using a modified viral vector, a form of gene
therapy, can also improve the condition of the mice, and they
feel that this may be translatable, in time, to a therapy for
RTT patients.
One of the challenges associated with this approach is
delivering the gene to the brain without further damaging
cells that are already functioning poorly.
An alternative approach might be to deliver the gene to cells
of another organ that is not amongst those functioning
particularly poorly in patients (e.g. the liver), and have that
organ produce molecules of the MeCP2 protein and send
them to the brain, where they may be taken up by brain cells
and used by those cells - a form of what is called ‘protein
replacement therapy’.
The current project aims to develop the resources needed to
test this question and start investigating whether it looks as
though it can work in the knockout mice.
As ever, Dr Bailey and Dr Cobb are very grateful for the
funding that RSAS has made available to them so far.
BOOK – Rett Syndrome:
Therapeutic Interventions
Those of us who attended the RS Europe meeting in
Edinburgh in 2010 were very impressed by a talk given by
Meir Lotan on physiotherapy for Rett people.
Dr Alison Kerr, who has years of experience with Rett
people, has contributed to the book and highly
recommends it as being useful to our families.
Because of this the Association has kept in touch with
Meir and he has advised us that a book which he has
helped to produce is now out in a paperback version.
RSAS has ordered two copies which will be made
available to members to borrow. Our medical adviser,
When the book is received it will be reviewed and
further details will be given of how it could be useful to
you in the upbringing and challenges that you face in
your role as parent / carer of a Rett person.
Grateful thanks to John and the boys at
adprint for all their help.
Music Therapy Booklet
by Caroline Groves
As the Association has run out of the booklet “Music
Therapy in the Treatment of Rett Syndrome” and with the
importance of music in the lives of our Rett people, the
committee decided that a new and updated booklet should
be produced.
The music therapy day, postponed from last year, took place
at St Anne’s Church, Corstorphine, Edinburgh on Thursday
4th April. The therapy sessions were run by Janette
Montague, music therapist, with John Slavin, photographer,
on hand to capture the moment.
Individual music therapy sessions took place and also a
group session. This was then followed by lunch, with time
for the families and professionals to socialise afterwards.
Janette and John will now cooperate to produce the
booklet and it is hoped that copies will be available in the
autumn.
A big thank you is extended to the families / carers, Rett
people and professionals who attended on the day.
RSAS WEBSITE
Rhiannon Thompson has now taken over the running of the RSAS website and has been busy updating it.
Please visit www.rettsyndromescotland.co.uk to view the new-look site and let us have your feedback on
how you would like to see it develop and if you have anything you would like to add to the site.
Annual General Meeting 2013
The AGM took place in the Premier Inn, George St. Glasgow on Sunday 23rd June 2013
Despite difficulties accessing the hotel due to the National
Cycling Championships taking place in the surrounding
streets, which had been closed to vehicles, all those who
wished to attend were able to get through eventually.
Due to business commitments Gordon Weir has had to step
down from the committee this year, but the Association is
grateful to him for his support.
Pauline McQuillan has agreed to join the committee and it is
hoped that she will be co-opted on at the next meeting. The
remaining committee members were re-elected.
Accounts
The 2012 – 2013 Accounts have now been independently examined and passed to OSCR
The Accounts for the year 2012 – 2013 have been independently
examined and have been accepted by OSCR (Office of the
Scottish Charity Regulator). Further details of the accounts
will appear in the next issue of the newsletter.
General discussion of the accounts took place at the AGM
but will be discussed more fully at the next committee
meeting. However, it was pointed out that donations were
down by almost 50% from the previous year’s accounts, from
£3,451 to £1,761. This could be due to the money raised from
the relay, over £4,500, or a sign of the times.
The cash and bank balances stood at £59,001, compared with
£66,686 the previous year. A very rough estimate of annual
income/expenditure was a deficit of £10,000, including
funding of research and the cost of the Family Weekend.
The committee regularly discusses the budget and continues
to agree that both these items are of significant benefit to
our families and also uphold the aims of the Association.
However, with finite resources and at the current rate of
expenditure the Association will only be able to continue in
its current form for another five years approximately.
This problem continues to raise its head and once again the
committee will contact members for their views on the
continued existence of the Association in its current form.
Meanwhile, if you have any comments that you wish to make
to the committee, please contact the secretary.
REGIONAL ROADSHOW
Rett UK has contacted us to suggest hosting a Regional
Roadshow in Scotland in collaboration with RSAS.
Weekend at Badaguish. They envisage holding a professional
symposium for medical / health professionals.
They are chasing funding for the event, but have suggested
that perhaps it could coincide with next year’s Family
We will keep you informed of progress.
Coast to Coast Relay for Rett 2013
and the inaugural Coast to Coast Ultra for Rett 2013
by Caroline Groves, Secretary
The team members who took part in this year’s Coast to
Coast Relay for Rett 2013 and David McMahon who was the
first person to complete the Coast to Coast Ultra for Rett
2013 are to be congratulated on their efforts.
Day One, Largs – Bell’s Bridge
David McPhee and his girlfriend, Victoria, who last year took
part as members of the Bank of Scotland Aspire Team, again
made the trek to Largs to start the Relay. David ran and
Victoria cycled and both completed the first leg. The
weather was glorious, with the sea like a millpond. The pair
completed their six mile section at Fencebay, where they
handed the baton on to new mum Carina, who carried it up
the very steep hill to the Dalry Moor, with its fabulous views
across the Firth of Clyde to Arran and the Mull of Kintyre.
Here she passed the baton on to her 5 months old baby
daughter Caireen and together with granny (RSAS secretary,
Caroline) the baton was “buggied” the next short section
before Caroline continued by bike into Dalry where the trio
paused for a well-earned lunch, before cycling to
Lochwinnoch. Our Chairman, Graeme, covered the next 17
miles, walking to Johnston, where he jumped onto the bike
and cycled into Glasgow, to complete the first day of the
Relay at Bell’s Bridge.
Day Three, The Falkirk Wheel – South Queensferry
The weather had improved a bit by Sunday morning,
although it was still damp and misty. Kate and Angela had
continued their holiday on the barge and welcomed aboard
the first leg participants. These included their friends John
and Susan, Angela’s brother, Richard, his girlfriend, Morag
and Caroline. The barge was crewed by Oscar and Brian,
volunteers with the Seagull Trust.
The barge left the basin at the start of the first leg of this
section and was lifted from the Forth and Clyde Canal by the
Falkirk Wheel and on to the Union Canal, where Oscar and
Brian handed over the navigation to Richard and John, who
luckily managed to avoid sinking it!
The trip along the canal was wonderful, with some
astounding scenery, yet close to built up areas. John and
Susan had provided us all with delicious soup and
sandwiches and lunch was eaten on board when we had
moored at the Seagull Trust Boathouse.
From the boathouse Richard took over the baton from
Angela and cycled the 17 mile leg into South Queensferry,
without mishap (at least nothing he told us about), where he
handed the baton on to Muriel. Muriel and Angela,
accompanied by Anne, Janet and Kate then walked /
wheelchaired to cross the finish line and complete the last
leg of the Coast to Coast Relay for Rett 2013.
But that’s not the end of it!
Day Two, Bell’s Bridge – The Falkirk Wheel
Baby Caireen and Carina had volunteered to start the second
day of the relay at Bell’s Bridge, but the baby had been
unwell so instead Caroline walked that section to
Kelvingrove Park. Here she met up with Audrey O’Brien and
her friend Chiréne on their bikes. Some of you may
remember Audrey as being a carer for Jane Lees at one time.
Audrey has stayed in touch and continues to support the
Association.
The weather on the second day of the relay couldn’t have
been more of a contrast to the previous day. It dawned cold,
grey and dreich and as the day progressed it got worse, with
torrential downpours making cycling on the towpath of the
Forth and Clyde Canal treacherous, as the flooding masked
the uneven surface underneath. Luckily Audrey and Chiréne
managed to avoid cycling into the canal, although they did
carry safety ropes just in case.
The two girls cycled the complete section from Kelvin Grove
Park to the Falkirk Wheel, a distance of about 24 miles.
By the time they arrived at the Wheel, wet and cold, the rain
had stopped and Kate and Angela welcomed them aboard
their holiday barge, which had been specially adapted by the
Seagull Trust. Audrey and Chiréne donned plastic bags on
their feet and sat on bin bags to avoid soaking everything
that they came into contact with. Graeme had already
reached the barge and he set-to making hot chocolate with
marshmallows all round.
The girls had intended to cycle back along the towpath to
the start of their section, but it was decided that, due to the
adverse weather conditions it would be more sensible for
them to get a lift back, so they and their bikes were loaded
into the cars for the journey home. Well done to both of
them for a sterling effort.
Coast to Coast Ultra for Rett 2013
Last year some of the participants who took part in
the Relay felt that their section had not been enough of a
challenge and had suggested that they would like a
greater test of their fitness and endurance. It was decided
that this year we should offer entrants the chance to
complete either a one-day section of the Relay or the
chance to cover the complete 85 + miles. Several people
were keen to take up this new challenge but unfortunately
the dates didn’t suit, so it fell to David McMahon to be
the first person to participate in the inaugural Coast to Coast
Ultra for Rett.
Unfortunately for David he chose the worst day
weather-wise to take up the challenge and set off on
Saturday 18th May from Largs.
Apart from getting lost in Glasgow, having problems with
the surface water on the towpath and suffering from near
hypothermia, David managed to safely complete the whole
distance in one day to receive the first ever Ultra medal.
What a tremendous achievement.
An enormous thank-you goes to those who took part and to
those who have sponsored the participants.
Special thanks go to D Mackay, Manager of Timpson, Largs,
who acted as starter for the Ultra and also to Fencebay
Smokery for allowing us the use of their car park as a
changeover point. Also to Kate and Angela for allowing us to
use their holiday barge when the original Seagull Trust barge
was out of action.
SPONSORSHIP MONEY FOR THE
RELAY HAS NOW REACHED £500
WITH MORE TO COME!
DAY 1
Largs to Bell’s Bridge
Carina, David, Victoria and Caireen at the
changeover at Fencebay Car Park.
Carina arrives at the summit of the
Dalry Moor…
…and hands the baton to Caireen for
the next leg.
DAY 2
Bell’s Bridge to the Falkirk Wheel
Graeme, Chiréne and Audrey, sheltering
from the rain at the canalside, Twechar.
The brave duo arrive at the end of
the stage at the Falkirk Wheel.
Drying out on the barge (note the polybags
on the feet and the bags on the settee) with
Angela, whilst Graeme makes hot chocolate
with marshmallows in the galley.
Chiréne and Audrey receive their
medals from Angela.
DAY 3
Falkirk Wheel to South Queensferry
Views from the barge.
The view from the top of the Wheel.
Angela, Kate, Richard, Morag, John
and Susan on board.
Brian & Oscar looking relaxed as
Richard takes the wheel and Susan
and John watch.
Angela presents medals to Kate,
Susan and John at the end of the
barge section.
Richard ready to set off from the
boathouse…
…and pedaling the towpath.
Angela passes the baton to Richard.
Richard, Morag and Susan
nearing the end.
Brian and Oscar with
their medals presented
by Angela.
Kate, Angela, Muriel, Anne and Janet
crossing the finish line.
Whilst abseilers descend from the bridge, Richard, Morag,
John, Angela and Kate wear their relay medals and David
wears the first ever Ultra medal.
Last year, following committee discussions, it was agreed that membership of RS Europe would be of great benefit to our
Association in its stated intentions “to work with other organisations to secure the best interests of children and adults with
Rett Syndrome and their families.” It was therefore decided that RSAS should become a member of RSE,
with its connections to Eurordis and Rare Connect.
Chairman, Graeme Dallachy, therefore attended the General Assembly of Rett Syndrome Europe
in London in November 2012 as representative of RSAS.
Twenty other representatives attended together with researchers Angus Clarke and Laurent Villard,
both of whom addressed the meeting.
The summary of Laurent Villard’s report is shown below.
Rett Syndrome: What’s Up?
Rett Syndrome Europe General Assembly - London, 17th November 2012
The presentation was divided in 3 sections dealing with basic research, translational research
and networks/meetings.
by Laurent Villard, PhD
I - BASIC RESEARCH
1. MECP2 IS GOING GLOBAL
The understanding of what is Mecp2 really doing inside the
brain cells is rapidly evolving. Initially, Mecp2 was thought to
repress (and possibly activate) transcription at the gene level
through binding to methylated elements in the vicinity of a
small subset of target genes. Currently, based on the work of
the laboratory of Adrian Bird (UK), MEPC2 is rather believed
to regulate the expression of thousands of gene, genome
wide. Indeed, it was calculated that the MECP2 protein was
abundant enough in the nerve cells to replace histone H1, a
protein that structures the DNA molecule globally.
Hence, rather than regulating the expression of a selected
subset of genes, MEPC2 is now thought to regulate the
whole DNA molecule in neuronal cells. This regulation of
gene expression inside each cell is of paramout importance
because cells need specific sets of genes to be expressed in
order to achieve its development and function. Obviously, a
sperm cell and a neuron need different proteins to be built,
although their DNA is identical. This differential expression
of proteins is made possible through proteins such as MECP2,
among others.
2. MEC2 MAINTAINS MATURE NEURONAL NETWORKS
The group of Nurit Ballas (USA) recently described that the
loss of MECP2 in the adult stage of the disease (in the mouse)
was causing brain shrinking. The dendritic arborization
(contacts of neuronal cells with neighbouring cells) becomes
less complex. This finding suggests that MECP2 is necessary
to maintain mature neuronal networks and reinforces
the notion that the protein is not necessary during the
development but rather, is necessary when neurons reach
their final differentiation stage.
3. WILD TYPE MICROGLIA ARREST RETT SYNDROME.
This is the recent work of Jonathan Kipnis (USA). Glial cells
are "maintenance" cells in the nervous system. They insulate
neuronal connections (oligodendrocytes), feed neurons
(astrocytes) or clean debris (microglia) among other
functions. A significant amount of data supports the idea
that glial cells, in addition to neurons, play a role in RTT.
Indeed, MECP2-deficient astrocytes cannot support normal
growth of wild type neurones; the rescue of MECP2 in
astrocytes improves the disease phenotype and MECP2
deficient microglial cells were shown to be toxic to neurones.
Microglia are the macrophages of the brain. They originate
from bone marrow. Jonathan Kipnis and his colleagues
suppressed immunity in RTT mice and subsequently injected
wild type bone marrow (intravenously). Wild type microglia
were detected in the brain of the injected animals after a
period of time. The lifespan of the grafted animals rose from
8 to 44 weeks of age, their brain size increased and their
growth was normalized within 4 weeks of transplantation.
Tremors were suppressed by transplantation, gait, motor
and breathing abilities were also improved. A similar
improvement was observed for treated RTT female mice.
However, late transplantation (i.e. when the disease in
installed) only results in modest improvements.
Why such an effect of microglia? A diffusion of MECP2
between wild type microglia and disease neurons was ruled
out. Rather, is it proposed that wild type microglia could
better sustain growth factor secretion (e.g. IGF-1) or allow a
better clearance of (physiological) debris.
4. MECP2 CANNOT COMPENSATE ALL MUTATIONS.
The phenotype of the MECP2-null mouse (no MECP2 protein
produced) can be rescued by post-symptomatic activation of
MECP2 (work of Adrian Bird and others). However, a large
proportion of RTT girls are not complete nulls and have
missense or other types of mutations possibly allowing the
presence of an abnormal MECP2 protein. A study reported as
a poster at the annual meeting of the American Society of
Human Genetics (ASHG november 2012) by Juan YOUNG
(Miami, USA) reports that there is no improvement of the
phenotype when MECP2 is introduced in a non-null context
(a mouse harbouring a truncating mutation). According to
this work, there is a possibility that mutant MECP2 protein
interferes with wild type protein and prevents reversal
of the phenotype.
5. A RAT MODEL FOR RETT SYNDROME.
The SAGE initiative (Sigma advanced genetic engineering)
reported the creation of a rat model of RTT. The RTT rats are
completely devoid of MECP2 protein. These animals are being
sold by SIGMA. The advantage of the rat above the mouse is
that this model is much more suitable for social and behavioral
exploration, its brain can be studied more easily with electrophysiology devices and it lives longer than a mouse.
II - TRANSLATIONAL RESEARCH
1. OUTCOME MEASURES
Valid outcome measures are needed for RTT clinical trials.
Two interesting options were discussed at the World Rett
Syndrome conference (june 2012, New Orleans).
Infrared monitoring (F. Symons, USA)
Body temperature is usually identical on both sides of the
body. A study performed on 5 RTT patients showed body
temperature asymetry (in hands and feet, up to 10°C
difference). This non invasive measurement could be used to
measure efficacy of treatments targeting the autonomic
nervous system.
Pupillometry (PP. Patwari, USA)
Pupillary contraction is controlled by the autonomous
nervous system. Its measure is non invasive, quantitative and
rapid. It is used in Ondine’s disease and proposed to be
used in RTT.
RettBe (W. Kaufmann, USA)
RettBe is an initiative aiming at developing a behavioral
rating scale for children affected by RTT (3 to 18 years). The
cohort size will be 350 patients The rating scale will be
distributed to the RTT community at large.
2. ONGOING TRIALS
IGF-1 (Boston, MA, USA)
Information lacking... (a new PI is in charge). A group in
Houston (J. Neul) reported that a modified version of IGF-1
(supposed to be improved) at no effect at low dose and was
worsening the disease at high dose.
Desipramine (France, 6 centers)
32 patients have been included in a total of 36 patients. Since
it is a double blind trial, results will not be available until all
participants have been treated (the trial length for each girl
is 8 months).
3. ACTIVATION OF THE BDNF RECEPTOR WITH DHF
BDNF is deficient in the RTT mouse. Increasing BDNF levels in
the RTT mouse improves the disease. BDNF itself does not
reach the brain very efficiently and cannot be used directly.
DHF (dihydroxyflavone) supposedly activates the BDNF
receptor. It is a new molecule.
Contradictory results were obtained in different groups with
positive (Johnson et al. 2012) and negative (Villard, Roux,
unpublished and RSRT, personal communication) results.
4. BDNF TRAFFICKING AND CYSTEAMINE
BDNF is an important growth factor necessary for neuronal
function. BDNF is regulated by Mecp2 and is deficient in the
"RTT" mouse. HTT (the product of the huntington's disease
gene) regulates BDNF trafficking in the axons. The group of
Marseille (L Villard / JC Roux) showed that HTT was deficient
in the RTT mouse. Cysteamine improves BDNF trafficking and
delivery. It is used on clinical trials with Huntington's disease
patients. Data from the french group shows that cysteamine
improves the phenotype of the Mecp2-deficient mouse.
5. GENE THERAPY
Most gene therapy protocols now use adeno-associated
viruses (AAV) as a vector to deliver the gene therapy agent
inside the cells. AAVs do not cause disease, they infect
dividing and non-dividing cells and they do not integrate.
The group of Stuart Cobb recently reported that AAVs can be
useful to treat MECP2 deficient mice. The used the AAV9
serotype, containing MECP2 and injected into MECP2-null
neonatal mice (intracranial). Median survival of the treated
animals was 16.6 weeks instead of 9.3 weeks for untreated
animals. Locomotor function, exploratory activity and
neuronal volume were all significantly improved. Breathing
deficits were not improved, however.
Later on, when the treatment is performed at 4-5 weesks of
age, the effect is much more modest. The issue is likely to be
efficient delivery of the vector to the nerve cells.
III - NETWORKS - MEETINGS
EuroRETT funding is over but the group is still active. There
is one major achievement to maintain: the database (cf.
Angus Clarke presentation at the meeting). A group of RTT
clinicians was also built, independently from EuroRETT, called
ESSRA. There is no connection to EuroRETT (despite several
requests) and no participation to the european database
(despite several requests).
Concerning meetings, the next RTT european conference will
be held in Maastricht (NL) in October 2013 and the next
World Congress could be held in Moscow in 2016.
Graeme, third from left, at the
RSE Conference November 2012
EURORDIS
European Organisation of Rare Diseases
Through membership of RS Europe, Rett Syndrome
Association Scotland is represented at Eurordis.
EURORDIS is a non-governmental patient-driven alliance of
patient organizations representing 561 rare disease patient
organizations in 51 countries.
The European Organization for Rare Diseases (EURORDIS) is
the voice of 30 million people affected by rare diseases
throughout Europe.
EURORDIS is a non-governmental patient-driven alliance of
organizations and individuals active in the field of rare
diseases in Europe.
EURORDIS represents over 500 rare disease patient
organizations in more than 50 countries, covering more than
4000 rare diseases.
EURORDIS supports the creation and development of rare
disease national alliances and disease-specific European
federations and networks.
EURORDIS is supported by its members and by the AFM Téléthon, the European Commission, corporate foundations
and the health industry. EURORDIS was founded in 1997.
EURORDIS is widely recognized in Europe for its
achievements and as a main partner working with the
European Commission, the European Parliament, the
Council, the European Medicines Agency, EUnetHTA and
other stakeholders, including Orphanet, the European
Federation of Pharmaceutical Industries and Associations
(EFPIA), the European Biopharmaceutical Enterprises (EBE),
EuropaBio, and others.
EURORDIS received the Abbey S. Meyers Leadership Award
of the National Organization for Rare Disorders in 2010.
Yann Le Cam and EURORDIS received the Drug Information
Association President's Award for Outstanding Achievement
in World Health in 2013.
EURORDIS MISSION:
To build a strong pan-European community of patient
organizations and people living with rare diseases.
To be their voice at the European level and to fight against
the impact of rare diseases on their lives.
Further information can be obtained by accessing:
www.eurordis.org
FORTHCOMING EVENTS
Badaguish Family Weekend
Friday 9th August – Monday 12th August 2013
At present we have eight families attending this fun event, which offers archery, canoeing, abseiling and cycling using
specially adapted equipment and supervised by professionals. We are also hoping that there will be other activities taking
place over the weekend. Accommodation is in luxurious, adapted lodges and catering has been organized. If you think you
might be interested in attending please contact the secretary as soon as possible.
Rock the Rovers
Sunday August 25th 2013
Rock the Rovers is an annual music festival held in Kirkcaldy and organized by supporters of Raith Rovers Football Club to
raise money for local charities and the football club. Founded in 2005 the event has earned a reputation as being the
number 1 music event in Fife, with bands from all over the country – and some even further – playing at the one day event.
TICKETS FOR ROCK THE ROVERS ARE NOW ON SALE, PRICED £10.
There will be 20 acts playing on two stages at KITTYS and KANDY in Kirkcaldy throughout the day of Sunday August 25th.
A friend of one of the organizers has a Rett daughter and so one of the chosen charities of this year’s event is to be Rett
Syndrome Association Scotland. It is hoped that a cheque for £500 will be presented to RSAS in September.
The Annual Charities Christmas Fayre, Glasgow,
Tuesday 12th November 2013
Please note the change of day from the traditional Wednesday to the Tuesday.
The Fayre will take place as usual in the Banqueting Hall at Glasgow City Chambers from 10 am – 4 pm.
Please contact the secretary if you are able to help on the day or if you have items that can be sold on the stall.
European Rett Syndrome Conference
Maastricht, The Netherlands
17th – 19th October 2013
This year the conference “Research Update and Preventative Management” is taking place in Maastricht.
The main goal of this conference is to bring together a group of world-class scientists, researchers, clinicians, practitioners
and stimulate multi-disciplinary international cooperation. The aim is to also provide therapists, parents and caretakers with
a toolbox that includes the latest information on treatment of symptoms.
General topics:
Treatment and clinical management
Adult Rett and Ageing in Rett syndrome
Family education and awareness
Genetics and Neurobiology
Brain and brainstem physiology
Sleep
Cognition & Communication
Nutrition
Orthopaedic
Moving research into policy and practice
Rare disease initiatives in Europe and overseas
Case studies
MECP2 duplication, FOXG1, CDKL-5, etc
The conference in London 2012 was considered to be very worthwhile and it is hoped that a
representative from RSAS will be able to attend this year’s event.
If you would like to attend please contact the secretary for further details as soon as possible.
DONATIONS
As always our grateful thanks to all who have supported the RSAS by their
fundraising and donations. Without your help we would not survive.
Donna and Frank (via Tom and Martha Duncan)
Mrs M Chivers, Ledbury
Jack Cleary, Newlands (Two donations)
Violet Lesenger, Kelso, on behalf of her late sister-in-law,
who had a Rett grandchild in Australia
The Dove Trust on behalf of an anonymous donor
Belinda Davies, Ledbury
John Patience, Dingwall
Tom and Martha Duncan, Glasgow
Emily Liu, East Kilbride
Mr & Mrs G Shooter, North Mansfield
Joan Phillips, Milngavie
Ann Warnock, Broughton
K Yule, Aberdeen
Mr & Mrs J Cuthbertson, Hamilton (Two donations)
in memory of their darling granddaughter, Jenny Rankin
Nigel and Rosemary Marshall, Grange Over Sands
Margaret McGregor, Banff, (Two donations)
Avril Shanks, Bonnyrigg
Avril and Edward Griffiths, Tonyrefail
Frances Binnie, Prestwick
Jackie Cleary, Neilston
Pam Bellis, Port William
Mary McNicoll, Inchture
Paul Glover, Galloway Stoves and Chimneys
(via Hazel & Allan McKean)
Dr Alison Kerr, Bridge of Allan
FUNDRAISING
Catriona Stirling organised two fundraising days, one in 2012 and one in 2013, for colleagues at her work at Lloyds Banking
Group at Edinburgh, Sighthill. The “Dress Down Days” also received matched funding from the Bank of Scotland Foundation
Martha and Ray Henderson, Glasgow, held an “afternoon tea” fundraiser.
Hazel Mackay, Buckie organised a quiz to raise funds for RSAS.
CHRISTMAS FAYRE
Donations were received at the Fayre from:
Mary McNicoll, Inchture
Alice Cleary, Neilston
Jacqui Cleary, Neilston
Frances Binnie, Prestwick
Ellen, Kirkintilloch (via Joan Phillips, Milngavie)
COAST TO COAST RELAY FOR RETT 2012
Sponsorship money was received via Just Text Giving
COAST TO COAST RELAY FOR RETT 2013
Nancy & Derek McIver, Aviemore
Arlene Brown, Reading,
via the online Charitygiving website, which includes Giftaid
Audrey O’Brien, Glasgow,
via the online Charitygiving website, which includes Giftaid
Tony Cartwright, Faversham,
via the online Charitygiving website, which includes Giftaid
Joan Phillips, Milngavie
John and Susan, Edinburgh
Anonymous (via David McMahon, Edinburgh)
Anonymous (via Kate McMahon, Newtonmore)
P Groves, West Kilbride
D & S Nicholls, Ashkirk
Ann Warnock, Broughton
COLLECTION BOXES
Anne Morrison, Ochiltree
BIRTHS
Tom (committee member) and Martha Duncan are pleased
to announce the arrival of their grandson, Brodie, a
brother for Lucy.
Caroline (secretary and treasurer) and Peter Groves are
pleased to announce the arrival of their first grandchild,
Caireen.
Their daughter, Lisa, gave birth on 14/12/12 to an 8lb 6oz
baby.
Their daughter, Carina, gave birth on 28/12/12 to an 8lb
1oz baby girl.
Christmas Fayre 2012
We had another successful fundraising stall at the
Charities Christmas Fayre in Glasgow. Many thanks to
Joan for organising it this year and to everyone who came
along and helped on the day and to those who donated
items and / or bought goodies from us. A total of £333
was raised for Rett Syndrome Association Scotland
Thanks must also go to two “knights in shining armour”,
who went to the aid of the secretary on her way to the
Fayre, when her car (containing stock for the stall) broke
down.
Frances Binnie, flanked by her daughter, Alison and
granddaughter, Nicola, together with Joan and Jacqui.
Firstly, the gentleman from Highfield Heavies who diagnosed the problem and was able to make a temporary
repair enabling her to drive to Glasgow and also Graham
Steadman, General Manager of M8 Recovery, who
personally drove her and the stock to the railway station
to enable her to deliver it to the Fayre and then collected
her from the station to return her to her car.
Chivalry isn’t dead!
Lucy, with Star the RSAS mascot at the Charity Christmas
Fayre 2012, Glasgow. Lucy is the granddaughter of committee
member, Tom and Martha Duncan.
ABOUT RSAS
Founder/Honorary President
Mrs Isobel Allan MBE
15 Tanzieknowe Drive
Glasgow G72 8RG
Chairman
Mr Graeme Dallachy
‘Creitendam’
For Information & Enquiries contact:
Secretary/Treasurer
Mrs Caroline Groves
‘Blackthorn’
12 Ailsa View, West Kilbride KA23 9GA
Tel: 01294 829100
Email: [email protected]
www.rettsyndromescotland.co.uk
Committee Members
Jan Hunter
Anne MacLeod
David Jackson
Kate McMahon
Tom Duncan
DISCLAIMER
This Newsletter reflects individual’s views and
opinions for which no responsibility or liability
will be accepted by the R.S.A.S.
THE RSAS NEWS WELCOMES ARTICLES AND
COMMENTS FROM ALL INTERESTED PARTIES
ON ANY ASPECT OF RETT SYNDROME. PLEASE
GET IN TOUCH IF YOU HAVE NEWS, IDEAS, OR
A STORY TO SHARE. WE WOULD BE DELIGHTED
TO HEAR FROM YOU.
Rett Syndrome Association Scotland
is a Scottish Registered Charity: Number SCO16645