Whenever I hear the words "MD Breakthrough', my heart skips a beat. Is it really? Often, it is in reference to a study in the mdx mouse. We can cure mice. But people are not mice... just ask Victor Dubowitz. And when the 'breakthrough' talks about a young man with Duchenne, it feels like we are all standing at Attention!

Over the last couple of days, many of you have seen a news story that recently aired about a young man named Ryan. I wanted to share with you my thoughts about this story. For those of you who have not seen this piece, check out the story by following this link: http://www.kake.com/home/headlines/69538137.html.

I have watched the video of Ryan (by Jemelle Holopirek) several times and admit to some skepticism. To be quite honest, I have a lot of skepticism. My own sons were in the myoblast transfer trials of long ago, receiving some extraordinary number of donor myoblasts in their major muscles. It did not work, not at all. There was a moment when I thought I saw something, when Chris and Patrick did something or said something that seemed to suggest improvement. But there was nothing. And I used the same words "feels better," "seems stronger," etc. All generalities that cannot be measured.

I admit to some bias and for that reason, I wanted to get some answers. I have called the 800 number for Dr. Neil H. Riordan, the specialist featured in the story who is working from Costa Rica, and I am waiting on a return call. The number is answered in the US, and the person answering promised he would relay the message and have them get back to me.

Conceptually, stem cells make sense. The goal would be to deliver sufficient numbers of stem cells, to all of the muscles in the body, or at least the major muscle groups and make sure they integrate with existing muscle cells. The would potentially replace what is lost and if all that works, one might expect, over time, to see improvement.

But - and there is always a "but" - I have any number of questions.

We know this is difficult. Myoblast transfer trials were done in the late 80s and 90s. Jacques Tremblay continues with his myoblast transfer trials in Canda, now moved to limb delivery. Cossu (Italy) is moving toward limb delivery with mesioangioblasts. Gillian Butler Browne is working on stem cells. Lee Sweeney has just requested a small amount of money from us to expand some of his stem cell work (adult-derived stem cells). Barriers to stem cell delivery have been discussed in a variety of forums over the years. For Duchenne, and many other conditions, stem cells are suggested to be the Holy Grail, but it just has not been as easy as hoped for. Some years ago, we sponsored Marie-Therese Little at the Fred Hutchinson Center in Seattle, working on stem cells in the dog model. The barriers included identifying the specific type of stem cell, engineering it to ensure it would make muscle, delivery and rejection. And what does the immune suppression protocol look like? Loads of questions and progress for sure, but not magic.

The video describes three treatments over a year and a half with 46 shots into every major muscle group that resulted in a muscle biopsy with "100% dystrophin levels."

As a community we have to ask the difficult questions. Some of them include:
* What muscle did they biopsy? How was the level assessed?
* What was Ryan's functional ability before the transplant? How has he improved? His wonderful friend Clint (thank heaven for friends like Clint!) described 'neck and trunk stronger' and 'balance better' and 'gained 30 lb.' On the video, Ryan moved only his hands/forearms. And increased weight may not signifiy increased muscle mass and circumference of a specific muscle does not mean increased strength.
* Muscle biopsy - who did the staining? Quantification of dystrophin?
* Transplanted cells - cells from Ryan's sister and donor umbilical cords. What is the immune suppression protocol? Any concerns regarding graft vs host rejection?
* Function: What tests pre- and post- were done to document benefit?

It seems to me Dr. Riordan would do well by convening a meeting with researchers and physicians, including leading experts in the field like Cossu, Gillian Butler-Browne, Terry Partridge, Lee Sweeney, Jerry Mendell, and others. He could then describe his research, procedure(s), data, and outcomes in detail answering a wide range of questions.

I hope I do not sound overly negative. But I have been through this with a wide range of treatments and promises made to our community. And my frustration is not with Dr. Riordan. I hope, just like all of you, that his work is the "breakthrough" this report claims it to be. I just wish the media would understand that words such as "breakthrough" should be used with caution because the reality is often different from the message, and it is their responsibility to ask questions and get substantiated answers before rushing on air.

I will try to contact Dr. Riordan again and look forward to talking to him and getting more answers for all of us. As always, I will share any information I get.

Warm regards,
Pat

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Comment by amit gupta on February 3, 2011 at 10:08am
I also talked to Michele Calos at Stanford and she said that 'Cossu is trying to start some trials in Europe, but it is early, and there is not too much chance of success'.
Comment by Lisa Mancin on February 3, 2011 at 1:30am

Amit, Thank you for the information.

Comment by amit gupta on February 2, 2011 at 1:02pm
Pat you mentioned about Dr Tremblay - i talked to him and he said that no progress has been made in the last 5 years on this since Health Canada will not give him permission to do any human trials. He said he'd try again this year and needs $200,000 for his clinical trial...I tried contacting Dr Cossu and he has not responded...so at least two of the projects that you mentioned don't seem to be going forward or have gone forward.

Staff
Comment by Pat Furlong on November 26, 2010 at 6:49pm
Hello again, none of us have given up on cell therapies. There are projects going on in many labs - Kunkel/Harvard; Sweeney/U.Penn, Cossu /Italy, Tremblay/Canada (to name a few) and broad projects with biotechs across the world. While it is true and wonderful that families take things into their own hands, the only way therapies will be available for all is to have the evidence. And the first step in Ryan's case is diagnosis. And once we have a diagnosis, we may better understand how to evaluate any benefits. There are many questions and few answers at the moment. Lisa, we are all hopeful stem cell therapies will progress and all of us would like nothing more than treatments and a cure.
Comment by Lisa Mancin on November 26, 2010 at 6:35pm
Thanks again Pat, but I must say that if the only thing holding back further research into this treatment is an accurate diagnosis, PPMD would do anything necessary to obtain it. Even if Ryan should have limb-girdle and not Duschenne's I personally feel that his results justify further research and clinical trials to see if cell therapy might apply to the Duschenne community.
Stem cell therapy is alive and well in this country. It is currently being used to treat many conditions. It is an exciting and growing field and many believe that it is THE future of medicine. WIth all due respect, Stem cell therapy will continue to progress, whether PPMD decides to jump on the train or not. There are several American (U.S.) doctors who are treating DMD patients in other countries. These families, like Ryan's, have decided to take things into their own hands, as they do not have time to wait on an accurate diagnosis or fact sorting. They have done what they feel is right and necessary for their sons and their families and should not be judged. Unlike Ryan's family they are not prepared to handle the negative comments and scrutiny that comes along with sharing their information. Pat, I truly appreciate all you do and hope that someday, in this country, stem cell therapy will be the cure (not treatment) for Duschennes.

Staff
Comment by Pat Furlong on November 26, 2010 at 5:41pm
Hello Again, I know Sharon was working on this and sent a mail today to all of them (sharon, bob, curt, sandra) to check on this. You are right, we spoke in summer. I'm not sure why the 'accurate diagnosis' has not been made. As I understood it, the family was to secure some of the cells from Athena.
Lisa to answer your question, I'm not sure we could pay for the testing as this would be discussed (you can imagine, there are many circumstances where paying for testing is requested), but I do think Jerry Mendell would be interested in testing. Jerry has considerable interest in Limb-Girdle muscular dystrophy and I think it is best to start there and ask questions. If there is a major hurdle, we can discuss how to handle it at that time.
All of us want the best for Ryan and pray for breakthroughs in cell therapy. I just don't think we can jump on this train until we have all the facts sorted out.
Comment by Lisa Mancin on November 26, 2010 at 5:01pm
Hello Pat, Thank you for your thorough explanation. It was what I was expecting you to say and I totally understand. So, I guess the next question would be, why hasn't the the "accurate diagnosis" been made yet. I understand that the test is quite expensive, but maybe in this unusual circumstance PPMD could pay for it. This way you could have the answers you need and you could determine the next step. Obviously, it is up to Ryan and his parents to decide if they want to do the test, but I am guessing they might. I understand that your meeting with Ryan and his parents was months ago.
Comment by cheryl cliff on November 26, 2010 at 12:01pm
As always Pat, you are throughly seeking the details of what is going on and I for one extremely appreciate your effort in this very difficult issue. Awhile back Paul and I had the pleasure of meeting Curtis Renard and found him to be a wonderful guy and caring step-dad for Ryan. Although we didn't realize, at the time we met him, there was any possiblity for a different dx for Ryan I now find myself in a morbid mindset of actually "hoping" (god & Ryan please forgive me) we are looking at dmd. If Ryan does have dmd it would be the only way any of this will end up benefitting the rest of our community. But I know you will get this sorted out and fast because I know you want nothing more than to see our sons thrive!

Very glad you are by my side. Couldn't do this without you.
best,
cheryl

Staff
Comment by Pat Furlong on November 26, 2010 at 9:08am
Hello Lisa, Please understand we have pursued this with the family and with Dr. Riordan. Ryan was diagnosed with DMD on clinical symptoms - weakness, etc. His actual mutation was not found. His original biopsy may have had dystrophin as well, so some of our discussions centered around needing a concrete diagnosis. Ryan discussed the fact that pre-transplant he had stopped physical therapy... for years. But when the opportunity for this procedure presented itself, he initiated an aggressive physical therapy regimen, and discussed how this also helped his appetite and overall health. We have concrete evidence to support the fact that aggressive (passive range of motion, swimming, etc) provide benefit. In discussions with his Ryan and his parents, we all agreed that it would be worth discussing this with Kevin Flanigan/Jerry Mendell because Ryan may actually have one of the limb-girdle dystrophies and not Duchenne. Dr. Riordan's paper 'reports a case of a 22 dmd...." because that was the original diagnosis, done 15+ years ago and based on clinical symptoms. The technology for molecular diagnosis was not available at that time. It is now. And we are finding that some individuals originally diagnosed have been misdiagnosed. As you can imagine, 15 years ago, doctors see boys who are clinically weak (abnormal gait, gower, wheelchair in the teens, etc) all were diagnosed as DMD. So, before we are able to pursue anything of this nature further and given what we know about cell transplant (types of stem cells, engraftment, immune response, etc) we first have to have an accurate diagnosis. I know this is all frustrating and all of us want/need this to work.
Long ago, my sons participated in a cell transplant procedure. Theoretically it makes perfect sense, replacing 'bad' cells with 'good'. In addition, some of my career was spent in the area of whole organ transplant. It simply is not easy. Further the biopsy was not zero to normal. The family sent us Ryan's biopsy results.
Lisa, I appreciate what the article suggests, but just because this appears in a journal is not sufficient to say it is fact. Dr. Riodan is reporting a case. As you might imagine, the scientific community may have a different opionion. I also know this is extraordinarly frustrating and heartbreaking because we all want something to work. I am sure Ryan and his family are thrilled with whatever they see as progress. But N=1 and no molecular diagnosis is insufficient evidence.
Sharon Hesterlee, PhD, Bob McDonald, MD (board member of ppmd, physician, son with dmd) and I spoke with Curt, Sandra and Ryan. We discussed at length biopsy results 1989, 1994 and 2009. diagnosis '89 made on 'abnormal tissue and clinical symptoms, no mention of dystrophin', 1994-could not find the mutation in the dystrophin gene. 2009 tested for dystrophin (improved diagnostics and ability to quantify dystrophin, which was not available in '89) Lisa, we are all anxious for concrete answers and hope.
From the first day my sons were diagnosed with Duchenne, I wanted to look under every rock, look at everything possible, take advantage of opportunities, do whatever it takes to leverage additional money. This is our focus. Sharon/Bob and I believe we have done our best to understand what is going on. Now we need an accurate diagnosis. Since no mutation was found, it is critical to understand if Ryan is the 0.5% of individuals where no mutation is found OR if Ryan has another type muscular dystrophy. And once that is determined, we would be in a better position to understand what is going on with Dr. Riordan's approach.
PS. I also have a copy of the paper.
Comment by Lisa Mancin on November 25, 2010 at 9:01pm
Hello Pat,
I have a copy of the Journal of Cellular Immunology where the article was published. In the first paragraph of page 5 of the article it states "We report a case study of a 22 year old male diagnosed with DMD at age 3, who manifested a progressive decrease in muscular strength and became wheelchair-bound at age of 12.
I will never understand why PPMD will not pursue this further.

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