No strangers in Bangalore: Muscular Dystrophy Conference

Deb Robbins, Parent Project Australia, reports on the first Asian PP Conference in Bangalore, India. I love her down-to-earth, funny, and wise-beyond way of looking at things.

Over 500 delegates attended the First Asian DMD Conference organized by United Parent Projects Muscular Dystrophy, Health Care Global Foundation and NIMHANS at St John’s Auditorium in Bangalore. Parents also came from Iran, Israel, Sri Lanka, Italy, The Netherlands and France. Stakeholders around the world were able to view the lectures via live streaming organized by Duchenne Parent Project Italy. International spectators were able to send chat questions to be answered by the panels along with those from the conference floor.

This was no local seminar but a national conference boasting an international program. Prof Jean-Claude Kaplan, Dr Annemieke Aartsma, Dr Madhuri Hegde, Debby Schrans for Dr Hendriksen, Dr Raghavendra Rao, Dr Lakshmi Raman and Dr Herve Laouenan explained their research. Dr Rao’s reasons for the suspected value of yoga for Duchenne were particularly innovative. Clinicians included Dr Nathalie Goemans from Belgium, Dr Jes Rahbek from Denmark, Dr John Bach, Dr Karim Wahbi and Prof Douglas Biggar. Though only one therapist presented, 160 practitioners attended Helen Posselt’s workshop.

Everywhere was evidence of dedication –the geneticists in Dr Lakshmi’s lab giving up their leisure time for family fun days and disseminating information to doctors surgeries on weekends. And no problem was any trouble for Dr Rao, the local organizer, to solve.

Particularly inspiring were the calls to rally together to abate the progression of Duchenne for one and for all, by Dr Ajaikumar (HCG), Dr Elizabeth Vroom (Conference Convenor & UPPMD President) and Hafiz Issadeen from Sri Lanka. All presenters urged parents everywhere to be proactive in both care and advocacy. With better care and promising research around the corner, it is more important than ever to plan for longer and more comfortable lives for our children than we could have imagined 15 years ago. The Parent Project Muscular Dystrophy group of India was inaugurated at the end of the two day conference and these core parent advocates networked with presenters and UPPMD stakeholders on the last evening.
In Bangalore as at home, I enjoyed swapping practical care tips and the trials and blessings of life with DMD, with other parents. More than one parent asked me to read specific medical information about their child confusing me for one of the doctors. They were desperate for more information though we’d just sat through hours of presentations. Yet the children and youths running, waddling or wheeling around the auditorium were as serene and ‘wise-eyed’ as Australian, European and American boys confirming my own theories about just who is saving who?

TRAKE STORY

My son, Pete, is 26 years old and now has his own blog (like mom like son!). He gave me permission to reprint one of his posts. It is about his take on getting a trach or trake. See his post below and then click on the title above and it is linked to an Aug 07 post of mine that I wrote about what I was going through at the time ...
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Ok, I'm going to spell trake wrong in this blog because the correct spelling does not look right. So if no one has any questions, we can continue.

Before my trake surgery a couple years back, I had the craziest question growing like a tumor on my brain -- will I still be able to sing after this?

Lets take a detour from the story for a moment for some backstory. I started writing and occasionally performing hip-hop lyrics at the age of seventeen. Part way through my sophomore year at St. Andrew's in Laurinburg North Carolina, my lungs were getting weak, too weak. This meant, after a pneumonia and a hospital stay that my out-of-State college career was over.

During this life-transition I made one of another kind. A transition from rap to rock. The band and I both noticed, the Summer leading up to the surgery, that it was getting harder and harder for me to belt out lyrics. Naturally horrified, I thought, with a trake that'll really be it! My singing days were surely numbered.

Or were they?

The recovery after the surgery was hell, taking all of three months of going in and out of the E.R., getting MERSA and a hole in the lining of each lung. I was told two weeks, ha, what a joke! I couldn't talk at first and having a cuffed trake didn't help either. Without explaining it in detail -- cuffed equals no sing, un-cuffed equals sing.

After re-learning how to talk and getting a cuffless trake, I must say that singing has become much easier. So after all the pain and hospital stays, I'd say getting a trake was the best decision I ever made! It saved my life and my voice.

Toshifumi Yokota and exon-skipping in the dystrophic dog

Toshifumi Yokota, a young man with a winsome smile and a bright future, is changing the face of translational research in duchenne dystrophy. Working with the dystrophic dog, he is our morpholino, exon-skipping expert. Toshi, as we call him, is the first author on the recently released Annals of Neurology article that is causing a sensation in the duchenne advocate and science world. This article shows the first multi-exon skip and the first large animal proof of concept (see March 15th blog and CNMC press release for details. See also videos of dogs with and without treatment)

Trekking back and forth between Kodaira, Japan, where his animal research is based and Washington DC, where he does bench work and analyzes data, Toshi is part of the team responsible for making sense of what the morpholino research is telling us. Working at Children’s National here in Washington DC, Toshi has access to the one of the leading scientists in duchenne research today. He is mentored by Eric Hoffman, a member of the original Harvard team that discovered the dystrophin, the mutant gene causing duchenne dystrophy.

Toshi ‘s work is crucial to the future of duchenne dystrophy clinical trials and development of a first treatment for our boys. Among the questions he and the research teams will be answering are:

• What are the optimum number of exons to be skipped at one time?
• The large dose of morpholinos given to the dogs is nontoxic. Can we be assured there will not be a toxic response is the clinical trials?
• How about with petide conjugated or vivo-morpholinos?
• What is the minimum dose necessary to have a therapeutic effect?

Toshi’s mother and father came from Northern Japan and they moved to Tokyo where Toshi grew up. He went to Tokyo University and majored in Zoology. In graduate school, he studied under the mentorship of Dr. Shin’ichi Takeda, MD, PhD. Toshi was eager to work with Dr. Takeda because of his stellar reputation and because his lab was known for its leading edge research work and state of the art equipment.

Toshi met his wife-to-be, Rica, at University over a decade ago. Married last year on Guam, the newlyweds live in Odenton, Maryland.

Exon-skipping in the dystrophic dog - good news

Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs

Good news in duchenne research. An Annals of Neurology article released March 13th shows that exon-skipping with morpholinos rescues “dystrophin expression to therapeutic levels” in the duchenne dystrophy dog (on-line 2009). It also shows that multiple exons can be skipped systemically. Toshifumi Yokota (pictured above) in Eric Hoffman’s lab and fellow scientists across the globe eked out meticulously researched findings in this seminal work.

The research reported by this study was a collaborative effort by Eric Hoffman’s Research Center for Genetic Medicine Lab, Children’s National Medical Center in Washington DC, Qi Lu’s McColl-Lockwood Laboratory in North Carolina and Shin'ichi Takeda’s Department of Molecular Therapy, in Japan.

The duchenne dog study shows that:

• Multiple-exons (three) had to be skipped in order to compensate for the deletion in the duchenne dog.
• Doses were 120-200 mg/kg delivered weekly or bi-weekly for 7 to 11 doses. (A similar dose will likely be required to be effective in clinical trials.)
• Intravenous morpholino cocktail showed no toxicity.
• The dogs treated with morpholino therapy ran faster than they did before the treatment while their untreated litter-mates ran slower.
• 26% increase in dystrophin expression levels in average compared to normal animals.



Please see the CNMC press release and the Annals of Neurology article itself for more information about the study.

Contributors donated millions to make this research possible. All I can say is, Thank you! Thank you! Thank you! The contributors include:

Foundation to Eradicate Duchenne (FED; www.DuchenneMD.org),
Department of Defense CDMRP program
Jain Foundation
Crystal Ball of Virginia Beach (Muscular Dystrophy Association
USA),
National Institute of Child Health and Human Development of NIH

These are not faceless organizations I look at this list of contributors and I see the Woods, the Heils and the Carsons from FED. I see Plavi Mittal from the Jain Foundation. And I see Linda Jarvis and her family from the Crystal Ball sponsored by the Muscular Dystrophy Association. Most are volunteers. They work, they take care of a son with muscular dystrophy, and then they make millions for muscular dystrophy research. And they do it for the same reason I put out this blog. We do it for our boys; James, Alex, Mark, Brian and Pete.

Qi Lu's Lab demonstrates the potential of Vivo-Morpholinos to treat duchenne dystrophy

In a new Molecular Therapeutics on-line advance publication released this week, Qi Lu's lab reported the potential of Vivo-Morpholino to treat duchenne dystrophy. Qi Long Lu, Director of the McCool-Lockwood Laboratory for Muscular Dystrophy Research and one of the world's leading experts on exon-skipping with morpholinos, explained the significance of his research:

"Antisense therapy has been demonstrated with great potential to treat majority of DMD. One of the most critical factors for a successful treatment of DMD is the delivery efficiency of the antisense oligonucelotides to body-wide muscles.

Unmodified Morpholino oligomers can restore functional amount of dystrophin protein in skeletal muscles, but with limited ability to do so in heart. Using Morpholino modified with a peptide improves dystrophin expression significantly, basut peptides could cause immune response and potentially prevent long-term use in patients.

Therefore, in this study, the Morpholino is modified with a non-peptide polymer (Vivo-Morpholino) to reduce the risk of immune response and to achieve improved delivery. The results demonstrate that use of the polymer achieves very high efficiency in dystrophin expression both in skeletal and heart muscles. Further long term efficacy study will be required before the same modification can be considered for clinic trial to treat DMD."

An abbreviated abstract and link to the full abstract are found below.

Wu B, Li YF, Morcos PA, Doran TJ, Lu PJ and Lu QL. Octa-guanidine Morpholino Restores Dystrophin Expression in Cardiac and Skeletal Muscles and Ameliorates Pathology in Dystrophic mdx Mice. Mol. Ther. advance online publication, March 10, 2009

Dystrophin exon 23 carries a nonsense mutation in the mdx mouse. Using a Morpholino oligo targeting an exon 23 splice junction can cause the splice machinery to skip exon 23, allowing translation of functional dystrophin with an internal deletion; however, unmodified Morpholinos enter cells poorly and large doses must be used to achieve splice modification in the mouse tissues. Coupling a Morpholino to a guanidinium dendrimer moiety makes a Vivo-Morpholino. When injected into the blood the Vivo-Morpholino circulates through the organism and enter cells, altering splicing and producing functional dystrophin.

Today at the White House - A Victory for Stem Cell Research and My Brother-in-Law, Pete

Here is something a little different from my usual blogs.

Today, with the Executive Order I am about to sign, we will bring the change that so many scientists and researchers; doctors and innovators; patients and loved ones have hoped for, and fought for, these past eight years: we will lift the ban on federal funding for promising embryonic stem cell research. We will vigorously support scientists who pursue this research. And we will aim for America to lead the world in the discoveries it one day may yield.
Barak Obama, March 9, 2009 (White House Blog)

Today, President Barak Obama signed an executive order ending the ban on stem cell research. This is good news for research, the entire world, and especially people like my brother-in-law, Pete, who along with my sister, Terry, were at the White House today to see it happen. At the White House! How awesome is that?

Pete has Amyotrophic Lateral Sclerosis, diagnosed over two years ago. And ever since then he has fought for stem cell research funding. As he told me once, he talked to anybody and everybody who would listen. He was a one-man campaign for stem cell research in ALS.


The National Institutes of Health (NIH) plans to award $10.4 billion in stimulus funding to research in general to be spent over the next two years. At this time I don’t know how much of it will go to stem cell research but, with support from the President of the United States, it will be substantial.

These pictures are from my sister, Terry. She says the above picture of Barak Obama is really a picture of him shaking hands with Pete, but there was only room for one of them in the picture…

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