tag:blogger.com,1999:blog-83595632078600329742024-02-19T08:01:31.688-08:0079Anonymoushttp://www.blogger.com/profile/16004532217429066343noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-8359563207860032974.post-45307463163815637822015-10-17T09:05:00.000-07:002015-10-17T09:05:16.285-07:00NICE decision for use of Translarna - a criminal actThe decision this week from NICE in the UK to deny boys with Duchenne Muscular Dystrophy the use of the drug Translarna is criminal.<br />
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This first use of a genetic therapy for Duchenne has been <a href="http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002720/human_med_001742.jsp&mid=WC0b01ac058001d124" target="_blank">approved by the EMA</a> and other European countries have already agreed to fund the use of Translarna. In Scotland one young person, <a href="http://www.musculardystrophyuk.org/news/news/landmark-first-as-scottish-child-becomes-first-to-receive-translarna-on-nhs/" target="_blank">Cormac Fegan</a>, has been granted funding for Translarna.<br />
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Patients, patient organisations and UK clinicians have all recently presented a <a href="http://www.actionduchenne.org/nice-evaluation-committee-meeting-on-translarna-full-report/" target="_blank">strong case to NICE</a> for NHS England to fund this new medicine. Families have lobbied the Government and <a href="http://www.maryglindonmp.co.uk/muscular%20dystrophy%20June%2015.html" target="_blank">MP's</a> have raised the issue with the Prime Minister this week at PMQ's.<br />
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The decision making process for Translarna has been blighted for months by cancelled meetings and a lack of urgency despite the knowledge that delay in delivering medicines like Translarna affects the quality of life and possibly the life expectancy of young people living with DMD.<br />
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The current decision by NICE, to be further reviewed in November 2015, seems to be based upon a perceived lack of positive data that would make this drug cost effective. In other words NICE seem to be arguing that it is too expensive and does not cure or significantly reverse the severe muscle wasting associated with the condition over and above current treatments like steroids.<br />
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So what does the published data from PTC show? Is the decision made by NICE politically driven by austerity and budget constraints? How are the NHS in England going to manage the delivery of new experimental drugs for conditions like DMD?<br />
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This week <a href="http://files.shareholder.com/downloads/PTCT/868901402x0x854777/D3E48095-4972-4E6E-A533-E143B1090571/PTC_2015-10-15_ACT_DMD_slides_public_call_Thurs_5pm.pdf" target="_blank">PTC have published new data</a> relating to a Phase 3 clinical trial that follows data already presented to NICE and the EMA from a Phase 2b trial.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjx0VK9rAOLXUXPFjhJAr8nVwfCEnmkwdldrBISUwczLjFQXrIa_eD46PRySM6_miKR0TyQcjexOazReNTnX3huaFd5qo5bK6UIRYHaUir58mBgG3PjNo64x95erdrBH-bTCwGuIrCtfSU/s1600/translarna.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjx0VK9rAOLXUXPFjhJAr8nVwfCEnmkwdldrBISUwczLjFQXrIa_eD46PRySM6_miKR0TyQcjexOazReNTnX3huaFd5qo5bK6UIRYHaUir58mBgG3PjNo64x95erdrBH-bTCwGuIrCtfSU/s640/translarna.jpg" width="640" /></a></div>
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The overall ITT is not statistically significant for the 228 patients in the 48 week trial. But the sub group pre specified that walked for between 300-400m at baseline showed 47m benefit that is highly significant. There would seem to be a window of opportunity in administering Translarna for boys who are still ambulant and can walk more than 300m in 6 mins. Of course this does not mean that other boys could not benefit (see data below for the North Star analysis) but administration at this stage appears to be most effective.<br />
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This shows graphically how this group maintained 6MWT vs placebo. The drug seemed much less effective for boys able to walk <350m at baseline but still better than placebo. These Phase 3 results seem to replicate the previously submitted data from the phase 2b trial.</div>
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PTC have also used the North Star Ambulatory Assessment as a secondary endpoint. Families in the UK will be familiar with this assessment undertaken by expert physiotherapists at our Neuromuscular Centres. These assessments are wide ranging standardised measurements of muscle function and relate directly to the natural progression of the condition for individual patients. Boys showed significantly improved scores in both the overall group and more significantly for the 300-400m base line group.</div>
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This data from PTC for just 48 weeks administration of this drug is very compelling evidence.<br />
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NICE, however, are still prevaricating on making a final decision despite having access to similar data from the 2b trial and the conditional approval from the EMA. At several meetings that I have personally attended with NHS England and NICE the argument comes up again and again about the cost of this drug and the Governments budget for specialised medicines supposedly a paltry £340m. Translarna is a high cost drug. We have no information on the price to the NHS but figures from £100- 200K pa have been suggested. However the Government have had plenty of time to make plans for funding high cost drugs for rare diseases. The Charity <a href="http://www.actionduchenne.org/" target="_blank">Action Duchenne</a> has lobbied Governments on this issue since at least 2003. The <a href="http://www.musculardystrophyuk.org/app/uploads/2015/02/Access-to-high-cost-drugs-report-FINAL.pdf" target="_blank">APPG Muscular Dystrophy comprehensive report</a> for example was published back in 2013 but little has been done to plan for funding drugs like Translarna or the exon skipping drugs now going before the FDA in the US. The Government still has its head in the sand.<br />
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So the crisis of NHS funding in general stems from political choices. I don't remember there being much debate about bailing out banks to the tune of £500bn following the 2008 crash. However the <a href="https://you.38degrees.org.uk/petitions/fund-first-treatment-for-duchenne-muscular-dystrophy" target="_blank">support from families and the wider public is palpable</a> with over 25,000 signatures from a recent petition shows real public support for funding drugs for rare diseases like Duchenne in the UK.<br />
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The data so far published by PTC shows a real window of opportunity for boys to take Translarna. The drug would appear to be very safe and not have the significant side effects of cortiocsteroids the current drug of choice. The delays are criminal and can not be justified on the basis of cost. Boys will be losing ambulation and will miss this important window to get maximum benefit from this drug. NICE and NHS England have a duty of care to ensure these young people have access to medicines that could improve the length and quality of their lives.<br />
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Fund Translarna............... and the Government must do much much more to help to support the efforts of families, Duchenne Charities, our Neuromuscular Centres of excellence to continue to monitor and improve treatments so that one day we will see a complete cure for Duchenne Muscular Dystrophy.<br />
<br />Anonymoushttp://www.blogger.com/profile/16004532217429066343noreply@blogger.com1tag:blogger.com,1999:blog-8359563207860032974.post-70402675183262381722014-12-11T04:52:00.000-08:002014-12-11T04:52:23.686-08:00Carmeseal-MDAn early access programme was announced for Carmeseal-MD™ (Poloxamer 188, NF) recently (<a href="http://www.phrixuspharmaceuticals.com/news.php">http://www.phrixuspharmaceuticals.com/news.php</a>) with the headline:<br />
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"Phrixus<span class="Apple-tab-span" style="white-space: pre;"> </span>Pharmaceuticals announces European Access Program for CarmesealMD™ (P-188 NF) for<span class="Apple-tab-span" style="white-space: pre;"> </span>patients with Duchenne muscular dystrophy"<br />
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Treat NMD and UPPMD have published this very good guideline for families <a href="http://www.treat-nmd.eu/dmd/carmeseal/">http://www.treat-nmd.eu/dmd/carmeseal/</a><br />
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It is interesting to note here how it is possible to gain early access to medicines within current legislation for a drug that has not been tested in clinical trials for Duchenne. Again an excellent review of these procedures by <a href="http://www.treat-nmd.eu/resources/ethics/early-access-medicines-development/">Treat NMD</a> . It would appear that in this case access to Carmeseal would be on a "Special" "named patient" basis where the doctor would contact the company directly and take responsibility for administering a drug. It was not very clear in their press release if Phrixus have clinicians already in mind or if they expect patients to consult their own MD's.<br />
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The second issue is that there appears to be evidence from the Treat NMD review that Carmeseal-MD has side effects that might lead to muscle weakness. Phrixus also report that they are planning clinical trials in Duchenne patients.<br />
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It is worth keeping in mind that if a company chooses to offer their drug for use on the basis that it might do some good then individual clinicians can administer it to patients even without it having been tested in specific DMD clinical trials. In my own view the test should always be to consider if there is enough evidence to show that the benefits of taking a drug are more than likely to outweigh risks or side effects in the long term. This evidence might possibly come from animal studies, usage in other patient groups, clinical practice etc; but we know that clinical trials conducted in Duchenne patients are the best way to collect data to determine the benefit/risk ratio and establish the efficacy of medicines.<br />
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So it might be the case here that patients can find clinicians that Phrixus are willing to offer Carmeseal to for administration for Duchenne. If that is the case for you then look carefully at the research data highlighted by Treat NMD and ALWAYS first consult your own neuromuscular expert team before agreeing to take any new medication.<br />
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<br />Anonymoushttp://www.blogger.com/profile/16004532217429066343noreply@blogger.com0tag:blogger.com,1999:blog-8359563207860032974.post-84592700759238324942014-12-02T04:38:00.003-08:002014-12-02T04:38:46.498-08:00Open letter to Sir Nick Partridge Chair of CPAG<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="font-family: Arial; font-size: 15px; line-height: 1.15; white-space: pre-wrap;">Dear Sir Nick Partridge</span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">I have a son Saul who is now 14 and living with Duchenne Muscular Dystrophy. I still remember holding him as a little baby in a small room when the neuromuscular consultant told us that he had Duchenne. We kind of knew what this would mean. The muscle wasting is severe and now is affecting his everyday life. He told me the other day that any kind of drug would help just to stop him from being so tired everyday. Saul is studying hard for his GCSE’s and to his credit he has overcome some tough steps in learning to read to become a great student. He wants to design computer games or maybe be an archaeologist!</span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Unfortunately the new drug Translarna will not help him as he does not have the right gene variation for it to work. However this drug can help other young people living with Duchenne in the UK who might just not have to suffer such extreme muscle wasting that my own son has experienced. Also we know that other personalised medicines for Duchenne might be coming on stream through clinical trials currently in progress and so there are real prospects for treating most if not all the boys.</span></div>
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<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">So it is vital that the CPAG committee understand the need to fund Translarna and also other new medicines when they become licensed.</span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Saul suggested that I set up a petition </span><a href="https://you.38degrees.org.uk/p/translarna" style="text-decoration: none;"><span style="background-color: transparent; color: #1155cc; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: underline; vertical-align: baseline; white-space: pre-wrap;">https://you.38degrees.org.uk/p/translarna</span></a><span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"> and I’m delighted to say that the Duchenne Community and many others (including the dog Elvis!) are supporting our call to fully fund this treatment.</span><br />
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><br /></span></div>
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<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;"><img alt="20141129_142711.jpg" height="268px;" src="https://lh6.googleusercontent.com/bA9o-C7xngmkn958ISHF3BGv3w4-GSx5dCG1malNNFMTqmypSopPUhStL3terjuG4b87t2zoilh-qUivoUOG4RoDvzTjnBSUN0Zx0xdKg53uyKoh-AGHeSLsp2Bo92jQPA" style="-webkit-transform: rotate(0.00rad); border: none; transform: rotate(0.00rad);" width="201px;" /></span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Translarna and other drugs downstream can offer significant improvement in the quality and length of life for our sons. These drugs can keep young people out of hospital, freeing up beds and saving money in the longer term. However we know that they are still experimental and boys will need long term exposure to monitor efficacy and any side effects. </span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">The only way we can ensure that smaller pharmaceutical companies like PTC Therapeutics stay developing these personalised medicines for rare diseases is if they can see that they will get a reasonable return on their long term investments. So it is crucial that the NHS have a budget that is going to meet the costs of delivering these novel therapies.</span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Families have been waiting a long time for new treatments to come on stream and everyone in the Duchenne community urges the NHS in England, Scotland, Wales and Northern Ireland to fully fund the costs of Translarna and support its immediate delivery to patients.</span></div>
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<div dir="ltr" style="line-height: 1.15; margin-bottom: 0pt; margin-top: 0pt;">
<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Thank you for your support and please can you make sure that your committee members are fully aware of our growing petition now at over 10000 signatures </span><span style="background-color: white; color: #333333; font-family: Arial; font-size: 13px;"><a href="https://you.38degrees.org.uk/p/translarna">https://you.38degrees.org.uk/p/translarna</a></span></div>
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<span style="background-color: transparent; color: black; font-family: Arial; font-size: 15px; font-style: normal; font-variant: normal; font-weight: normal; text-decoration: none; vertical-align: baseline; white-space: pre-wrap;">Nick Catlin</span></div>
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2nd December 2014<br />
<br />Anonymoushttp://www.blogger.com/profile/16004532217429066343noreply@blogger.com0tag:blogger.com,1999:blog-8359563207860032974.post-13057249137343986922014-12-01T01:52:00.003-08:002014-12-01T01:52:29.496-08:00Funding Translarna means we still have hope<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0cm; text-align: justify;">
<span style="font-size: 10.5pt; line-height: 115%;">Was Rachel being a little paranoid when she said something
was wrong? Ben wouldn’t do the things she had read about avidly both during
pregnancy and after he was born. He missed milestones and we even moved house
so that he wouldn’t have to go to the tiny village school – we thought he
needed pushing more – so we moved and thought we’d solved a problem for our
‘laid back’ happy little boy.</span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">The date is etched in our memory. We’d gone to have a test at the
hospital, and despite a slight worry we went away for the night after the test
with Ben. We were carefree. Rachel was 3 months pregnant and we were doing ok.
Good jobs, nice house, you know the score. Returning home the day later we
listened to the answer machine (it was 2003) and our consultant told us to ring
her as soon as possible. The problem was it was 8pm. We rang friends and family
in a panic. They told us to calm down – it wouldn’t be anything serious. The
next day our world fell apart. Along with most other parents we had never heard
of muscular dystrophy, let alone Duchenne. <o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">We were told, like all parents of a child with Duchenne,
that our son would be in a wheelchair by the age of 11, we were told that life
expectancy was early 20’s and most devastating of all we were told there was no
cure. We staggered through the next few months and then, like many others in
the same position, life became almost normal again but with an underlying sense
of sadness. We found the Muscular Dystrophy Campaign on the internet and over
the years became involved with fund raising. We had to do something. The Great
North Run became an annual event for friends and family -it still is – and
Charity Balls raised tens of thousands. We were put in touch with others
parents and they put us in touch with PPUK – Action Duchenne as it is now. Suddenly
there seemed to be the slightest glimmer of hope. Drug trials and potential
treatments were being spoken about as real possibilities and for the first time
since diagnosis we allowed ourselves to believe that a treatment could be on
the horizon. We signed up to the DMD registry to ensure we would have a chance
to take part in any potential trial. When you have a child you never imagine
that you would ever consider putting them through a drug trial; when you have a
child with Duchenne it is an opportunity you grab because the alternative is
just too horrific to contemplate. We had followed the progress of PTC124
through numerous articles and speeches at the conference because we knew Ben
would be eligible if trials took place. <o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">Ben participated in the original trial for PTC124 aged 7
in 2008. PTC124 became Ataluren and more recently Translarna. Ben takes this as
a powder mixed with (in our case) water 3 times daily at intervals of 6 hours. </span><span style="font-size: 10.5pt; line-height: 115%;">Before the trial Ben was mobile and
only used a wheelchair for distances. <o:p></o:p></span></div>
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The trial was a double blind trial: both ourselves and the clinicians had no
knowledge of which boys were on the placebo, the low dose or the high dose. The
drug's purpose, as we understood it, was to read through the nonsense mutation
and this is why it would only ever be effective for around 13% of boys. We were
aware from a very early stage how crucial this trial was to the whole Duchenne
community. It was the first of its kind but because it only targeted some boys
our feelings of elation were tempered with feelings of guilt. Like all parents
we want to see an end to the condition for all our children.<o:p></o:p></span></div>
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Being part of the trial meant that Ben had to go to the study centre every 6
weeks. This meant an overnight stay due to the distance and the requirement of
fasting bloods early in the morning. Ben had a muscle biopsy before starting
the trial (and after 48 weeks) and throughout had to do various tasks and blood
tests, both for safety and efficacy. The main test was the 6 minute walk test
(6MWT) – measuring how far he walked in this time.<o:p></o:p></span></div>
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As a parent of a child with Duchenne you watch every move more closely. This
became even more intense as we watched every move looking for improvement. This
started the very first day after he took the drug for the first time. We
described the chance of participating in the trial to family and friends as
being so fortunate. They looked at us bemused in describing our days on the
train and frequent visits to see our son put through the demands of the trial.
It wasn't easy. It felt like living in a parallel world every few weeks.<o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">We thought we saw a difference quite soon after starting
the trial but of course we didn't know if Ben actually was taking the drug or
was on the placebo. So we were at first unsure whether he seemed to be
doing more because we wanted it to be working or whether he actually was
showing signs of improvement. Friends and family also began to comment on
things he was doing. </span><span style="font-size: 10.5pt; line-height: 115%;">As
the trial progressed Ben seemed to have the ability to keep going for longer.
He could not necessarily go faster but he didn’t stop so soon. On one
particular day in summer, when Ben was on the trial, we went to a farm with an
indoor soft play area. We arrived at the farm when it opened at 10.30 and we
did not leave until 3.30pm. Ben played in the soft play area at the beginning of
the day and seemed to cope more easily with the obstacles. Throughout the day
Ben walked around the farm – a huge incentive for Ben – but even keeping this
in mind he did keep mobile. At the end of the day Ben went back into the play
area and was able to, again, play with his brother. We had previously been to
many similar places and Ben had never done as much or stayed as mobile for as
long. At the time we were stunned and both discussed the fact that our day was
how we would imagine a “normal” family day out to be.<o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">Our world came crashing down when the trial was stopped
suddenly after 15 months. We had to hand over any drugs that were unused. How
could we give back something that was going to help our son walk for
longer? We were devastated - it felt almost
like Ben had been diagnosed with the condition again. We read every press
release avidly to try to see a glimmer of hope so that he could take the drug
again. We argued with clinicians about how it was working so well. We had found
out that Ben had been taking the low dose – the one that had been proved to be
more effective measured by the 6MWT.<o:p></o:p></span></div>
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In 2013 an extension trial finally started again. There is still the safety
tests and efficacy. The efficacy is largely via the six minute walk test and
North Star. <o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">We are fairly certain – although we can’t be 100% - that Translarna
has slowed down the progression of Duchenne in Ben. It’s like making sure you
put the best oil in your car. You know the car is getting older, but the parts
keep working for longer. He is doing very well at 13¾ - he is still walking
short distances. The rest of his 'care' is pretty good too. As a family
we try to ensure the other aspects of protecting Ben from the ravages of this awful
condition are maintained: nightly stretches and splints, he doesn't do stairs
as we have mostly lived in a bungalow, his diet is pretty good too. <o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">Being on a trial is such a roller-coaster. Your hopes are high but you never know what’s
around the corner. It’s tough, it’s emotional, but this is your child. We would
do it all again in a heartbeat. <o:p></o:p></span></div>
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As the drug has got closer and closer to being available it means other drugs
are closer to being available too. It increases confidence in the treatment of
Duchenne and paves the way for other trials to help all of those affected by
this awful condition. Translarna has given us hope – it’s given Ben hope. He
would rather not take this chalky drink 3 times a day, but he does because he
knows in his own small way that it’s giving him a chance to keep walking. Is
that too much to ask? Funding Translarna means he and others get that chance –
there’s not much else out there yet.<o:p></o:p></span></div>
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<span style="font-size: 10.5pt; line-height: 115%;">Please sign the petition set up by the Duchenne Community:</span></div>
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<span style="background-color: white; color: #333333; font-family: Arial; font-size: 13px;"><a href="https://you.38degrees.org.uk/p/translarna">https://you.38degrees.org.uk/p/translarna</a> </span></div>
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<o:p>Thank you for your support</o:p></div>
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<o:p>Bernie and Rachel Mooney</o:p></div>
Rachelhttp://www.blogger.com/profile/09368361428053316275noreply@blogger.com0tag:blogger.com,1999:blog-8359563207860032974.post-41601119720963525722014-11-27T07:25:00.002-08:002014-11-27T07:25:41.262-08:00Campaign for TranslarnaTranslarna is the first novel drug to be granted market approval for Duchenne Muscular Dystrophy that treats the underlying causes of the condition. <a href="http://www.ptcbio.com/ataluren">PTC Therapeutics</a> have been granted marketing authorisation in the European Union under the trade name Translarna™ for the treatment of Duchenne patients aged five years and older.<br />
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This is a crucial landmark in treating Duchenne despite only being targeted at a small sub population of children that are currently experiencing the severe muscle wasting effects of this condition. Young poeple will have to have a <a href="http://dmd79.blogspot.co.uk/2014/11/79.html">single point mutation</a> of the dystrophin gene in order for Translarna to have a chance of reading through the gene to produce a functional protein. Parents should check with the <a href="http://www.actionduchenne.org/registry/the-uk-duchenne-muscular-dystrophy-registry/">DMD Registry</a> at Action Duchenne if they are not sure of their child's genetic diagnosis or if their child might benefit from this drug.<br />
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Right now NHS England are considering whether or not to pay for the costs of this drug to patients.<br />
The <a href="http://www.muscular-dystrophy.org/research/news/7738_european_commission_grants_translarna_conditional_approval">Muscular Dystrophy Campaign</a> are heading up a campaign to get Translarna properly rolled out and funded.<br />
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But should we all be doing much more?<br />
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This will be a vital test case with the NHS in England, Scotland, Wales and Northern Ireland to see if they will provide substantial funding and support to offer treatment to a small number of patients with rare diseases like Duchenne Muscular Dystrophy. There are other potential therapies coming downstream for Duchenne and my fear is that in the current climate of cut backs and austerity that Translarna will not get funded. If that is the case then this will massively jeopardise access to other treatments downstream.<br />
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In the US recently Duchenne families and organisations united in a fantastic campaign with the FDA to get them to shift support for faster access to the exon skipping drug at <a href="http://www.sarepta.com/pipeline/exon-skipping-duchenne">Sarepta</a> .<br />
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We urgently need a united and vocal campaign from all UK Duchenne and Muscular Dystrophy Charities to win NHS funding for Translarna. We need to involve all parents, young people and families and mobilise them to contact our MP's and organise lobbies at the DoH. Winning this campaign is a vital step forward for new and better medicines for all our children.Anonymoushttp://www.blogger.com/profile/16004532217429066343noreply@blogger.com0tag:blogger.com,1999:blog-8359563207860032974.post-29377638028456746342014-11-27T04:52:00.000-08:002014-11-27T04:52:04.106-08:0079<div class="separator" style="clear: both; text-align: left;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSBd-eiHTRbvjfULmk_QAKu3IZc-7jzbS2ms-Q-9d1bXbS07hU1JCVM847ClSe7gPz7_xW-iCWS1mbaEAcRua_bahxMK2NDbckJvUm3QStRDC6YYzWfviW2nmMw8d6IRrZJPea3EnPl18/s1600/Duchenne.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSBd-eiHTRbvjfULmk_QAKu3IZc-7jzbS2ms-Q-9d1bXbS07hU1JCVM847ClSe7gPz7_xW-iCWS1mbaEAcRua_bahxMK2NDbckJvUm3QStRDC6YYzWfviW2nmMw8d6IRrZJPea3EnPl18/s1600/Duchenne.jpg" /></a></div>
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In the 1850's Guillaume-Benjamin-Amand Duchenne (de Boulogne) discovered Muscular Dystrophy. In fact, the original name of this disease was Duchenne Muscular Dystrophy, named in his honor.<div>
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But it took until 1986, for the gene dystrophin to be cloned, until we had a real scientific basis for understanding the mechanisms underlying the severe muscle wasting first seen by Duchenne over 130 years before.</div>
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It is very important to understand how mutations or faults in the gene result in a lack of protein called dystrophin being made to support the healthy growth and maintenance of muscle tissue.</div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhs5lpvH4cTtfh8OW2GP-bPEejVTKyrc43PdLMsnjE4hSepR0-C0bay5VM5uBO7sTaOr2O-L-_74vGCKqly3zWVtyyFsdJ0iDTMAz0X_JmhilhUnoG-80qp0inQlkuMJyb3ZpxDaZ5u-MA/s1600/engencodedisrupted.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhs5lpvH4cTtfh8OW2GP-bPEejVTKyrc43PdLMsnjE4hSepR0-C0bay5VM5uBO7sTaOr2O-L-_74vGCKqly3zWVtyyFsdJ0iDTMAz0X_JmhilhUnoG-80qp0inQlkuMJyb3ZpxDaZ5u-MA/s1600/engencodedisrupted.jpg" height="62" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">from <a href="http://www.humgen.nl/lab-aartsma-rus/index%20for%20parents.html" style="font-size: medium; text-align: start;">Dr. Annemieke Aartsma-Rus</a></td></tr>
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<a href="http://www.humgen.nl/lab-aartsma-rus/index%20for%20parents.html">Dr. Annemieke Aartsma-Rus</a> gives us all an excellent explanation of how genes in our chromosomes code for essential proteins like Dystrophin.</div>
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What is of real significance to understand is that mutations in this particular gene, the largest in our genome, results in a catastrophic loss of a protein that in the long term gives rise to severe muscle wasting and also in some cases cognitive problems.</div>
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Annemieke's cartoon of the 79 exons shows a deletion of exons in the dystrophin gene that will mean the information can not be read and translated into a functional protein.</div>
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At first it was hoped that the dystrophin gene could be simply replaced. However since 1986 it has become apparent that due to the size of the gene and it's widespread distribution in muscle cells around the whole body the task of replacing the faulty gene has been a far greater challenge than scientist first expected.</div>
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In terms of gene therapies a great deal of work has focused on finding ways and means of snipping out an exon (exon skipping) to make the gene readable or in the case of very small single base pair mutations to find a drug to promote read through of the gene. <a href="http://www.humgen.nl/lab-aartsma-rus/index%20for%20parents.html">Annemieke</a> explains this very well.</div>
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Where antisense drugs (AON's) put the exon gene sequence back in frame to produce a functional but shorter protein. </div>
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Or in the case of <a href="http://www.ptcbio.com/ataluren">Translarna</a> to read through a single point variation.</div>
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The use of <a href="http://hmg.oxfordjournals.org/content/11/20/2355.full#sec-4">viral vectors to deliver mini genes</a> are also now in development and moving towards clinical trials. This would essentially replace the gene that is not able to function with a mini gene, again due to the size of dystophin, that can produce a functional protein.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjbQ7-v1Lx1gji3NC2RG7McAE7YL5fH1jNOHPT3hc38LOkFky6dEwVpumqqshyphenhyphenPDgN4NPkMd1SE_bNpXt5d9O4xq8-14_eqe9g1wOZai7RJ9PXNPIl3CFiPyySsHk7jicZQFzp188023oo/s1600/Capture2.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjbQ7-v1Lx1gji3NC2RG7McAE7YL5fH1jNOHPT3hc38LOkFky6dEwVpumqqshyphenhyphenPDgN4NPkMd1SE_bNpXt5d9O4xq8-14_eqe9g1wOZai7RJ9PXNPIl3CFiPyySsHk7jicZQFzp188023oo/s1600/Capture2.JPG" height="146" width="320" /></a></div>
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Utrophin is a gene that is similar in the body to dystrophin and another potential therapy would be to up regulate utrophin so that it might be able to compensate for the lack of dystrophin.</div>
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Jon Tinsley explains <a href="http://www.summitplc.com/userfiles/file/2012%20Action%20Duchenne_Summit%20FINAL.pdf">Summits approach</a> with their SMT C1100 drug now in clinical trial.</div>
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There are other potential therapies and drugs in clinical trial and <a href="http://www.treat-nmd.eu/research/clinical-research/overview-current-trials-dmd/">Treat NMD</a> gives an excellent overview.</div>
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Progress is being made and our understanding since Duchenne identified the condition over 150 years ago has accelerated in the last 20 years. However only one novel medicine for Duchenne, Translarna, has gained market approval in Europe and only for a small group of patients. </div>
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