Interested In receiving a FREE copy? Email Tina Duong at tduong@cnmcresearch.org

May 28, 2008

SNAKE OIL SCIENCE - Let the Parent Beware

A good friend and president of Parent Project, Australia, Deb Robins, wrote a review of “Snake Oil Science” (2007, Oxford Uni Press) by R. Barker Bausell and I am delighted to share it with you. Deb's son, Doug, has duchenne and is attending college at James Cook University in Australia.

Please feel free to post your views on the book or the review. I'm going to go to my local library and check it out.

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Review by Deb Robins

I have just finished an interesting popular science book, “Snake Oil Science” (2007, Oxford Uni Press) by R. Barker Bausell, a research methodologist and once a director of research at the University of Maryland. He presents a very convincing argument by analysing a wide array of research papers purporting positive results in the field of alternative medicines and treatments. He has discovered that very few, even popular and widely accepted supplements and treatments, employed good science methodology or controlled their investigations for a myriad of effects, bias etc., particularly the placebo effect. He alludes more than once, that bad science is not the preserve of alternate medicine either.

It’s a very systematic, lucid and sometimes witty path to understanding, which he guides us along, and whilst most examples referred to general pain relief and acupuncture, it is pretty clear to me now that I applied a reasonable amount of snake oil to my son in my time, including acupuncture. I sometimes even felt guilty that our family budget could not stretch to some therapies or in some cases cope with the quantities recommended.

Amongst other explanations, Bausell looks critically at the business of medical journals, the professional pressures of scientists, the Hawthorn effect (a short-term improvement caused by observing worker performance. (Wikipedia)), an overall lack of statistical understanding, the tendencies of journals and mass media to prefer positive results and the lack of attention given by researchers to the natural history of pain or disease.

Of course he focuses on the placebo effect and when I think back to the temporary surges in Doug’s strength or other temporary positive reactions to this or that supplement, although of course there were not too many of those, I realize that I didn’t do a meta-analysis of supporting “scientific” studies and I certainly was no scientist conducting my own badly conceived trial with one participant. Although this is a pretty big factor in the development of our brains - the ability to see cause and effect but there just also happens to be a fair amount of coincidence involved, when we don't use the proper scientific method.

My one compensation is that the effects of placebo are very real physiologically, albeit for very different reasons than the chemical efficacy of the supplement for instance…and none of these things probably did any harm. I don’t feel alone in my stupidity when the author cites the majority of intelligent people including physicians and researchers who are likewise fooled. Why, Americans recently spent $500 million on magnets alone – imagine the spending upon more popular therapies? No wonder, when it is such good business to promote bad science!

Science as a subject has not been mandatory throughout a student's secondary education in Australia for at least the past couple of years. What hope have future generations against the bad science inspired by commercial interests and so many other factors? In fact, I don’t think Bausell is at all happy that the NIH recognizes alternate medicine at some level.

One nice thing about Prof Bausell, is his humanity and this tempers his criticism more than once. At the close of the book, he actually writes a procedure for choosing the best sham therapy in order to optimize the real benefits from the placebo effect! Now that’s a balanced guy. If I had to do it all over again, even today with very few efficacious medicines at hand apart from my son’s steroids and heart meds to boast about, it would still be essential for me to keep doing things that might improve my son or make him generally healthier. I probably wouldn't stretch the budget so far again perhaps? Hope is a good thing after all and it is anathema for any parent to do nothing.

I realize this was not a volume which even mentioned Duchenne, but it resonated with me and I have nearly (but not quite) accepted that perhaps double-blinded randomized clinical trials are not as heinous as I believed, but pretty necessary, especially in research that might only involve self-reporting or functional measurements. In my opinion, this is a really interesting read for laypersons who read a lot of medical articles, as many of us parents do.

May 17, 2008

Join the Sunday Chat From OZ About Bathrooming and DMD

I know it looks as though I’m the publishing arm from Australia Parent Project East but here is another blog from OZ about something I believe is important.

This invitation goes out to all older DMD men and their caregivers to participate in an Australia Parent Project chat about DMD and toileting issues.

As duchenne men live into their twenties, thirties and beyond, we are seeing more and more problems due to smooth muscle weakness in the small intestines and bowels and bathrooming issues. As yet it has not been adequately addressed by the medical community. Here, however, is an opportunity to chat with one occupational therapist that has, Mathilde Backhouse, OT.

And now, I’ll let Deb Robbins take over and tell you about it in her own words.

A reminder that our Sunday (May 18) chat will start @ 4pm AEST (NSW, Victoria, Qld, Tas & ACT) or 2pm (WA)or 3.30pm ( SA, NT, Broken Hill ) International participants please consult your time converter.

Our special guest this week is Mathilde Backhouse OT – "Getting the Job Done" Mathilde Backhouse is an awarded senior occupational therapist supervising the occupational therapy department across all of Montrose Access’ four Queensland offices. An occupational therapist for over 30 years, Mathilde supervises the traditional occupational therapy service, early childhood and young adult lifestyle and leisure programs. Her interests include bowel/bladder management and the transition to adult life. Mathilde’s investigations in these areas have been published and she has presented her findings at conferences at home and abroad. In 2006, Mathilde presented her paper; Voiding Patterns of boys with DMD – an Australian Study at the 4th International Meeting in Paediatric Neuromuscular Rehabilitation, in Denmark. Underpinning her vocation is a strong belief in keeping fit in order to conquer the physical and mental challenges of life.

In preparation for the chat, (although not strictly necessary) please download "A Practical Guideline - DMD & Toileting Issues." Please have a saved copy open on your desktop or have this document open in Internet Explorer (browser) in case we need to refer to it during the chat.

See you there with plenty of questions for Mathilde!

Instructions for New Chatters

For those who haven't tried the Parent Project Australia Conference Room before, you will need to download and install this conference room application to your desktop.

After that, each time you want to visit the conference room, you have only to click on the red conference room icon on your desktop - you don't even have to open your web browser. Once there, please login with your name and your location - you do not need a password. You will need at least a headset microphone to chat. Webcams also work.

We are trialing regular chats in the conference room on Sundays 4pm AEST so be patient with any teething problems. You can also arrange to chat at any other time with other stakeholders.

best regards

Deb Robins
www.parentproject.org.au

May 13, 2008

MAD MAX ... with duchenne

When did my son change from a cute little guy in rugby shirts and Dockers to some character out of a Mad Max movie?

When he stopped walking? In the nearly twenty years since then Petey’s added the requisite Mad Max-ish hardware -- leg braces, joystick, steel rod, respirator – as well as a few touches of his own as the tattooed, head-shaven, nose-ringed singer in a rabble-rousing band. In my mind’s eye, I see the desert race scene and air brush a wheelchair into the mix.

The world of duchenne is no longer one where you are urged to 'take your son home to die in peace'. Now it is college entrance exams, careers, family life and, God willing, a treatment.

My son, Petey, is somewhere in the middle of that continuum, the first wave of the change. Being a middle child myself, I know what happens in the middle - you get lost. Petey found an antidote: No pity. Push back. Mad Max.

My son looks at awareness videos like one on my site and thinks it’s weird to see parents scared that their kids might turn into … him.

But once upon a time, he was one of those kids and I was one of those parents. He’s different now and so am I … but not so different.

I want my son to not have duchenne but just as much, I want there to not be duchenne.

Failing that, I want a treatment.

May 9, 2008

DUCHENNE EXON SKIPPING REGISTRY: A PARENT'S PERSPECTIVE

There is much excitement over this week’s announcement from researchers in Belgium, Sweden, and the Netherlands beginning a phase I/II clinical trial to determine the safety, effectiveness and tolerability of antisense oligoribonucleotide therapy or AON.

Will this clinical trial determine whether AON therapy for boys with this specific mutation can restore muscle function in duchenne dystrophy?

Duchenne dystrophy is caused by mutations in the dystrophin gene. These mutations are usually deletions or duplications in the exon region of the gene. Science has discovered a way to bridge the mutation so that the gene reading machinery can do its job and make a truncated protein where before there was none.

Below, Deb Robbins, President of Parent Project, Australia, makes a compelling case for you to enroll your child with duchenne in a regional/country dmd registry. This way you will be notified when your child is eligible to take part in a clinical trial.

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All advocates really must urge everyone in the duchenne community to register in a regional/country dmd registry so that they can be ready for clinical trials, because finally now science is ready. They are working on a viable treatment.

It is time... and perhaps we can strengthen some of our boys a little more - every little bit of function is and has always been a gift. How my Douglas would love to be able to toilet and feed himself more effectively or hold his cards at poker better, or pinch me when I tease him!

I am not misled in believing that we can cure our boys today or even in the near future but in this lifetime, due to the advocacy of the parent-led groups and the investment in research and international treatment consortiums. We should be able to strengthen some [of our boys] further than the timeframe afforded so far by accepted corticosteroid therapy.

This is what I find most exciting and frustrating at the moment. It has been a long time, since Pat [Furlong] found me in outback Australia in 1996 and shared her knowledge as an older parent, but I know in my heart from our international strivings, partnerships and in some instances even "one-up-manship", that without the parent groups leading the way in seeking viable care, treatments and seeking out the most dedicated professionals; and without parents with both deep personal and professional knowledge of Duchenne, we would not have the glimmer of hope that presents itself today for a kinder life for our children and their mums and dads nor be privy to the wonderful expansiveness of equally stoical siblings, therapists, clinicians and researchers.


DMD REGISTRIES

actionduchenne dmd registry (UK)

Duchenne Connect (North America)

Treat-NMD patient registries for SMA and DMD (Multiple Countries)

FROM THE TREAT-NMD WEBSITE

If you are a patient (or parent of a patient) with DMD or SMA and would like to register in a TREAT-NMD registry, you should do this via the registry in your country if one is available. Click on your own country's flag below to find out more.

May 8, 2008

New Exon Skipping Clinical Trial Announced This Week

This week, scientists from Belgium, Sweden, and the Netherlands announced the beginning of a phase I/II clinical trial to determine the safety, effectiveness and tolerability of antisense oligoribonucleotide therapy or AON. This clinical trial will study the effects of skipping exon 51 in boys with duchenne dystrophy.

Duchenne dystrophy is caused by an out-of-frame mutation in the dystrophin gene. Exon skipping allows the reading frame to be restored, thus creating a truncated dystrophin protein associated with a milder Becker form of the disease.

The Netherlands and Sweden have already started to enroll patients. In this study, "an important parameter will be the presence of dystrophin in muscle biopsies. This clinical trial ... uses an [AON to remove] an unwanted segment of the faulty DMD gene product."
(Prosensa Press Release, May 5, 2008)

"In this study, we extend our recent success proving the concept of local dystrophin production to a study with systemic application to achieve widespread dystrophin expression in muscles. ", according to Gerard Platenburg, from Prosensa, the company that makes exon 51, the AON that is being tested in this study. (Prosensa Press Release, May 5, 2008)


PRESS RELEASE, May 5th, 2008
Prosensa announces the start of an international multi-center phase I/II clinical study with ‘smart drug’ PRO051 in patients with Duchenne Muscular Dystrophy.

May 6, 2008

Australia's Duchenne Community - Hopes and Struggles

Parent Project, Australia, PPA is five years old, and, as Deb Robins says, the 'baby' of the group [of muscular dystrophy organizations]. Deb, who heads up the Parent Project, Australia is also a part-time working mom with three grown-up sons, one with Duchenne , promoting PPA and the managing the website and … well, that's enough for now, isn't it?

In fact all the officers and grass roots members who support annual campaigns have jobs outside the organization and they have no paid employees . I find that pretty amazing since I have a hard enough time just keeping this blog going!

PPA offers many resources for the duchenne community. These resources include bi-annual national conferences for up to 300 people and providing funding for disadvantaged parents to attend, distribution of PPMD multi-media DVD's (all researched around the globe and produced in Queensland by the educational advisor to PPMD, Helen Posselt PT) , a web-cam/audio conference room for networking and an on-line library of duchenne pulmonary, cardiac and multi-discipline evidence based treatment articles and the latest news in research from exon skipping to PTC-24.

PPA has had only limited success, due to being voluntary with 2 annual fundraising campaigns and other fundraisers, but through grant writing has been able to provide dozens of cough assists, standing frames and beach wheelchairs to clinical partners in all states of Australia. PPA links to a 'care notebook' from Children's in Seattle, Washington – organizing all the patient care information from meds to doctor's appointments. In fact PPA doesn't invent the wheel due to time constraints but strives to alert parents to the wealth of Duchenne and Becker research occurring every month around the world. Deb wrote the foreword to the new website, Duchenne Community.This exciting and latest initiative of the UPPMD is virtually a Facebook for the Duchenne community and this website allows families everywhere in the world to establish contacts and share information and exciting research news. You can even initiate chats with other "dots" using the website at the same time.


PPA, as a struggling voluntary organization has had limited success in funding research in Australia but has partially funded a doctoral fellowship and some 'honors' awards to young scientists and therapists in duchenne research. The last three were presented in 2007 and collected further evidence about the effectiveness of new drugs upon heart, respiratory and skeletal muscle, the effect of exon skipping upon mutations and our sons' quality of life.


Deb and her executive committee have their work cut out for them as they take this fledgling operation to the next level: sustainability.


In fact, PPA is hoping that they can raise funds for decent research projects by forming a company with a new name - Duchenne Foundation and hopefully achieving a higher profile.


To this end, PPA is working on raising their profile and staging some higher profile events for awareness. Desiring to be economical and accountable they rely on a scientific advisory board, headed by Prof Andrew Hoey, in the confidence they can invest in the very best Australian and overseas research.


Their biggest challenge right now is to try and get funding for a DMD Registry. Registries are tools for research groups to find patients with specific gene variations and other clinical criteria for new Duchenne clinical trials.


As Deb puts it "how will we give everyone [in the duchenne community] the opportunity to participate [in trials] if we don't know all that have the stop codon mutations [or what exons are skipped]? With other orphan and smart drugs being trialed at the moment in the US and Europe, it won't be too long before there will be more opportunities to participate in multi-centre trials, which target more popular mutations. It is so vital that we strengthen our children at the earliest opportunities before precious muscle is lost. As we know, every bit of function preserved is precious and whilst we don't have to invent the wheel because of the global Duchenne registry, we do need the infrastructure in Australia to verify mutations and clinical information to participate fully. Multi-centre trials are the fastest way to verify efficacious treatment for all worldwide, so it is not an insular view.


Only one state has routine MPLA test, the other states only have the old hotspot analysis for many of the older boys . UK, USA and Italy invited PPA to use their portals to the global duchenne registry and we have a curator who has been to the meetings in Europe, but they don't have any funding to do the ethics submissions to approach all families to participate, test all those who have not had fine mapping, work with families who have given consent to verify the mutation and clinical information with the testing center and neuromuscular clinics ."


This is PPA's main priority at the moment because all of us want to keep our children in the best possible shape and we imagine there will be necessary delays in bringing burgeoning efficacious treatments to the market.


They must succeed and continue to provide support and service to the Australian duchenne community because only by concentrating on DMD as a separate disorder, can they make honest and realistic progress, which can in time inform research into other neuromuscular disorders. PPA believes in the power of synergy and without any clinical capacity, they choose to form partnerships with existing centers of clinical excellence so that their equipment can be prioritized and monitored properly by experienced professionals. PPA makes no apologies for their national focus on Duchenne because these children have comparatively so little time in the face of many high profile and lifestyle diseases, which do seem to be national priorities; but mostly because they have experienced the ripple effect every time they network with the global Duchenne family.

May 2, 2008

David Feder is fighting for a future: his son's

David Feder, his wife, Ana Lúcia Langer, and their three children; Leonardo, 23, Clarissa, 23 and Adriana, 19 live in São Paulo, Brazil in South America. Leonardo has duchenne dystrophy.

Both David and
Ana Lúcia are doctors. They were among a concerned group of parents who started Fight for a Future several years back to hurry along duchenne dystrophy research.

In Oct 06
, Fight for a Future hosted the translational research in duchenne dystrophy conference in Brazil (see Terry and Raju, August 14, 2007).

Earlier this week, David posted a link to the muscular dystrophy abstracts to be presented at the Annual Meeting of the American Society of Gene Therapy in May 08. This lead to an exchange of emails about the state of research and how frustrated we feel that it is taking so long to move forward to clinical trials.

I was struck by the simple eloquence of his words. David gave me permission to share his post and here it is, without embellishments:


Until this moment, the only good news has been for mice and dogs. No clinical trials.

Old teens and adults with duchenne dystrophy don't have time to wait for all steps of each trial. They want to run some risks and they want human trials now.

Young children have time to wait for more translational studies. They can choose safe therapies. However, because there are so many possible translational studies to go to clinical trials, it slows research down. Probably you know that the first study in mdx mice with gene therapy was realized in 1993. In the 15 years since then, no gene therapy trials have completed all 3 clinical trial phases.

There are translational research options that give good results:

• gene
  • micro-dystrophin
  • mini-dystrophin
  • full dystrophin
• follistatin
• myostatin
• and dystrophin
• IgF-1 and others
• vetor
  • adenovirus
  • CMV virus
  • HIV virus
  • plasmideo
  • chemical transporter and others.
• Promoters
• oligonucleotideos
• morpholino and others
• route
  • venous
  • arterial
  • only for heart and others

How many times do they need to choose the best options to start the trials? This generation [our son’s] don't have time for science.

They need therapy!

 
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