Rochester leads international effort to improve muscular dystrophy treatment

A large international study aimed at improving the care of muscular dystrophy patients worldwide is being launched by physicians, physical therapists, and researchers at the University of Rochester Medical Center.

Neurologist Robert “Berch” Griggs, M.D., is heading the study of treatments for Duchenne muscular dystrophy, the most common form of the disease that affects children. The condition, which affects boys almost exclusively, progresses rapidly. Boys’ symptoms start when they are toddlers; untreated, they end up in a wheelchair before they become teenagers. With today’s best treatments, the disease, which affects about 28,000 boys and young men in the United States, is often fatal by the time a patient reaches his 20s or early 30s.

Despite decades of research, Griggs calls the current treatment landscape for the disease “chaotic.” Recently he has identified 29 different treatment regimens in use by doctors around the world.

The new study is designed to eliminate the chaos. With at least $11 million in funding from the National Institute of Neurological Disorders and Stroke, Griggs and co-leader Kate Bushby, M.D., and investigators at 41 other institutions around the world will study the three treatments most commonly used today. The study will include 300 boys ages 4 through 7 throughout North America and Europe. Recruiting for the study will begin in the summer of 2011. Study funding is slated to reach close to $15 million.

The central feature of Duchenne muscular dystrophy is muscle weakness. The first symptoms, often seen around age 2 or 3, usually come when a boy has difficulty running, jumping, or climbing stairs. From there, even with treatment, the disease progresses very quickly. Boys are often confined to a wheelchair by age 9 or 10 because of weakness in their legs; their breathing muscles begin to fail and their heart muscle weakens dramatically in their teen years. Most patients begin receiving assisted breathing with a ventilator while they are teenagers.

About two-thirds of cases occur in families with a history of the disease — the genetic flaw responsible is passed from mother to son — but about one-third of cases occur spontaneously. That’s because the disease’s roots lie in a genetic flaw in the massive gene responsible for making a protein known as dystrophin, which helps make and keep muscles strong and stable. Weighing in at 2 million chemical bases, the gene is the biggest in the human body, and mutations are relatively frequent. In patients with a mutation, the body does not make enough dystrophin, and muscle fibers are gradually replaced with fat and other tissue.

In a study more than 20 years ago, in studies supported by the Muscular Dystrophy Association, Griggs and colleagues found that a daily dose of prednisone improves patients’ lives dramatically. Yet Griggs has found that the treatment for Duchenne muscular dystrophy is chaotic because of concern about side effects. In a recent survey of more than 100 centers worldwide that specialize in treatment of the disease, only three were consistently using the recommended treatment — a daily dose of prednisone. Others were using prednisone intermittently or were using deflazacort; 10 weren’t using steroids at all.

In the new study, patients will be randomly assigned to receive one of three steroid treatments: a) prednisone every day; b) prednisone every day for 10 days, alternating with 10-day periods without the drug; c) daily use of a steroid known as deflazacort, which is approved for use in Europe but not the United States. Neither the patients nor the researchers will be aware of the patients’ treatment assignments until the conclusion of the trial.

Doctors have found that daily prednisone boosts muscle strength dramatically and that the effects are felt by patients and witnessed by parents within just 10 days. The drug boosts muscle mass by 20 percent and slows the degeneration of the muscles in patients with the disease. But concerns over side effects leave many doctors leery of prescribing the medication on a daily basis. Side effects can include weight gain, behavioral effects such as hyperactivity or irritability, and eventually loss of bone and even possibly fractures.

“People have worried about side effects of daily prednisone, and many people have felt there must be a better alternative,” said Griggs, who is professor of Neurology, Medicine, Pediatrics, Pathology and Laboratory Medicine, and a member of the Center for Human Experimental Therapeutics. “Our study is designed to address exactly this question: What is the best balance between effective treatment and side effects?”

Children will be evaluated every six months for three to five years. Researchers will measure the breathing capacity of the patients, which is often an indicator of how long a patient will live; they will ask patients and parents how satisfied they are with the treatment; and they will measure how long it takes patients to stand up after lying down, which is an indicator of how long a patient will be able to walk.

“With a healthy child, if you clap your hands and tell him to stand up as quickly as he can, he’s up on his feet in less than a second. With a child with Duchenne muscular dystrophy, it might take 30 times longer,” said Griggs. “The child will roll onto his stomach, laboriously lift his bottom into the air, and slowly move his arms to one knee, then the other, bracing himself until he finally straightens up.”

The study brings together two worldwide groups of physicians who specialize in the study of muscle disorders. The Muscle Study Group, with nearly three dozen sites in the United States, Canada, and Europe, is based in Rochester and headed by Griggs. The TREAT-NMD study group is a consortium of dozens of institutions across Europe and elsewhere that work together to study neuromuscular disorders. TREAT-NMD is headed by Bushby, who is Action Research Professor of Neuromuscular Genetics at Newcastle University in the United Kingdom.

Bushby and Griggs are leading the clinical aspects of the new study. Michael McDermott, Ph.D., professor of Biostatistics and Neurology, and Rabi Tawil, M.D., professor of Neurology, are co-leaders of biostatistical analysis and data management.

The team from Rochester also includes Barbara Herr, assistant professor of Neurology, manager of the U.S. portion of the project; associate project manager Christine Annis; Shree Pandya, lead U.S. physical therapist; Mary Brown, Heart Research Program manager; William Martens, data manager; and Emma Ciafaloni, M.D., associate professor of Neurology, who will lead the study of patients in Rochester.

Griggs is central to the international effort to find an effective treatment for the disease. Last week, for readers of the journal Lancet Neurology, Griggs was asked to put into perspective new findings from a study of the drug cyclosporine, which recently proved safe but not effective for patients. Griggs also served as the head of the data and safety monitoring board for a study of an investigational drug called ataluren conducted by PTC Therapeutics; earlier this year the company announced that the drug, though safe, failed to help patients in the ways doctors had hoped. Analysis of those data continues.

1 COMMENT

  1. My name is David Summers of Murfreesboro, TN and I have had MS for 16 years. I am 37 years old and as of January 2012, was effectively an 8.0 on the EDSS scale. Originally RRMS, my disease progression had become SPMS (very progressive) within 4 years of onset. Normally anyone in my position and with my bleak diagnosis is limited to a short future, absolutely no quality of life and a painful end…possibly prior to my 40th birthday if the current progression of the disease continued (without the slightest hesitation or glimmer of hope, my Neurologist just told me: “ Prepare to deteriorate”). But after I heard about Dr. Zamboni’s ‘liberation therapy hypothesis’ in 2010, I began my search for the vein-widening therapy. This put me into a clinic in Duluth, Georgia where they were doing the liberation procedure. I received immediate positive results post-procedure…along with the surgeon’s warning that 50% of the MS patients who undergo the liberation therapy suffer a re-narrowing of the jugular veins within a year or so. Sure enough, within 3 months I knew that I was going to be among the unlucky 50%; all of the original improvements disappeared as I relapsed.

    I felt the only way forward was to get it done again, hopefully this time with more enduring results. But where would I go to get this done again and how would that be possible? If my neck veins restenosed after the first treatment, what was to prevent that from happening again…and again? I began to read the Internet blogs and forum chats placed on the many new CCSVI sites by MS patients about where to go and what their experiences were. In this respect, the Internet became a valuable educational tool for me. On several of the blogs, I discovered a New York clinic where they placed a stent during the procedure to keep the jugular veins open, and that positive results were being seen. Grimly, I also discovered that although rare, the prospect of death as a result of this procedure was also a risk. At least one person in a recent study had died when the stent migrated to his heart. But I was willing to put those thoughts and the risks aside. What did I really have to lose? I was dying a slow death. As long as someone was able to treat me there was a chance to hope, and I was down for it. But that wasn’t the main question I was asking myself.

    As my disease rapidly progressed and my disabilities became more overwhelming, the question I was asking myself was, was it too late for me? Although I was happy with the fact that my original liberation therapy had diminished most of the symptoms above my waist, I had to ask myself if getting stents was merely settling for a compromised improvement. Having had some success, if I had this done again, I wanted more! Don’t get me wrong, I think the liberation therapy is a miracle discovery from God. As soon as I had my first procedure my cog fog lifted, the vision in my right eye improved greatly, the numbness in both hands dissipated by a few degrees, my ability to taste food returned, my energy levels were ’off the charts’, and my sleep was so sweet. Also, because MS had robbed my body of the ability to regulate body temperature by sweating, I had not been able to handle the hot, humid Southern summers where I live, except to blast cold AC non-stop as a survival method during those sickly ‘dog days’. After the procedure this changed too. I knew it when deodorant suddenly became necessity for my personal hygiene once again!

    But it ended by the 90-day point and I was right back where I started. Immediately following the procedure I had dreams of rising from the wheelchair I’d been confined to for ten years and walking like a real man; but even with the incredible improvements overall, it seemed that the only healing occurred above the waist. Perhaps I would just have to accept that even if I could improve to what the full extent of the liberation therapy would allow, I would always be in a wheelchair. While researching the New York clinic and other places, my parents and I came upon CCSVI Clinic through a Google search. We discovered that they are essentially a research clinic operating under an IRB but with a major difference. For the past year, having seen even better results than just doing the liberation therapy alone, they have also been transplanting adult autologous stem cells, cultured and re-injected into the body shortly after the neck venoplasty. If I chose to go there instead of New York, the procedure would be done at CCSVI Clinic at Noble Hospital in Pune India and I would have to get there essentially as a partially paralyzed patient transported in a wheelchair. There would also be a requirement to stay in the hospital for 10-12 days. But after researching the improvements demonstrated in MS patients in stem cell clinical trials, I simply decided that as long as they would take me, nothing was going to stop me from making that trip. On calls with the clinic, it was also explained that stents were not necessary as the stem cells injected intravenously could be enough to keep my veins from restenosing. My confidence in their method increased when I discovered that Dr. Gupte, the neurosurgeon, had been transplanting autologous stem cells for 4 years for a number of different neurodegenerative conditions, including MS and based his therapies on completed stem cell trial methods done in a number of hospitals and universities outside of the US (to be absolutely sure, I confirmed this through searches on Google Scholar). He had already done over 2000 successful transplants! Regarding my communications with CCSVI Clinic, I need to confess here that we did not tell the doctors the truth originally. My mother, who arranged the treatments, told them that I was an EDSS 6.5 in order to qualify. Basically she knew that they wouldn’t accept me into the program if she said I was higher. But if they saw my actual physical condition could they refuse me on the clinic steps? I hoped not.

    So in late March it was off to India with my father who is a strong man, and my capable assistant. We arrived on March 26, 2012, and met Surjo Banerjee, CCSVI Clinic’s Managing Director at the airport. He drove us from the airport to Pune, a surprisingly modern city just south of Mumbai. I was amazed to see that the hospital and the CCSVI Clinic itself, (a full wing of suites within the hospital complex) was as clean and modern as any hospital here in the States. After checking in with a number of other patients, I was triaged for the procedures. However, based on my new assessment, it was determined that I would need about twice the amount of stem cells that they had originally programmed, figuring my EDSS scale requirement of 6.5. But paying more was out of the question. We are not rich and had basically ‘sold the farm’ to get here in the first place, and the recommended additional stem cells were going to cost another $12,000 that we had not planned for. Not their fault…I didn’t tell them the extent of my condition in the first place. So the first miracle happened when CCSVI Clinic management offered to personally cover these additional costs. I had never even met some of them, but as a result of their generosity, I received an additional 50,000,000 mesenchymal stem cells and I cannot thank them enough for the difference they have made to my life.

    On Tuesday March 27

    , I once again had the liberation therapy followed by the harvesting of red bone marrow cells from my hip bone. The clinic has strict aftercare protocols around each type of procedure with regard to position control and movement. It didn’t much affect my activity because I was unable to move much anyway. I was supine positioned, tilted slightly head high for two days following my venoplasty and then laid out supine again, in just the opposite tilt…head-lower-than-the-body for several days following the transplants of the stem cells. I was told that this would allow the newly transplanted stem cells to filter through the full length of the nervous system and locate to the points of injury. A Doppler ultrasound of my neck veins was done every day for 10 days following my liberation procedure. This was to check for any clotting or re-narrowing of the veins which had been widened. If they clotted or restenosed at any time I was in the clinic, they would take me back into the cathlab for a re-do. Happily this wasn’t necessary.
    Following the liberation therapy, the changes within my body were just as immediate and dramatic as in my first procedure in 2010, hopefully without the fear of re-stenosis; but my ‘headspace’ almost didn’t accept it. The first time with my liberation therapy in the US, the IR found one narrowing in each jugular, the right side being more severe. This time around, two blockages were found on my right side, and again one on the left. I have heard that second and third procedures for venous angioplasty are more difficult for the surgeons because there is more build up of scar tissue in the interior of the veins, but the medical team took their time and did a perfect job. Words cannot express the emotional joy in getting the blood flowing again and getting those symptomatic improvements back a second time!

    Four days later I underwent a lower lumbar puncture, but this time not simply to gather information on whether I have MS. This time, stem cells cultured from my own body were on their way to do what God designed them to do, and that is to heal. For all of you that might be skeptical about this, I am here to tell you that is exactly what they are doing. The positive changes were noticed as soon as I returned to my suite in the clinic and anyone who is paralysed below the waist will understand this next part. To manoeuvre myself as I usually do, I went to pick my leg up from a sitting position and throw it in front of me. The hope here is that the ‘dead-weight’ of the leg will land just right and in a position where I can best situate myself to haul my body into a position where I can further awkwardly throw my whole body into my wheelchair. If you’ve ever seen a spinal patient do this or are unlucky enough to have to do this yourself, you know what an ugly, uncomfortable process this is. But this time the ‘throw’ of the leg proved to be an over-compensation. To my absolute shock and delight my leg lifted itself just as it’s supposed to work…without aid from my helpful hands and placed itself exactly where my brain told it go! At first I didn’t think much of it…this was a fluke, maybe my imagination, but it was something sure not to last. But it has to this day without any hint of regression as I work out and get stronger. This was the first sign of any recovery whatsoever that has occurred below the waist in over ten years, and it happened only hours after the stem cell transplant!

    Upon returning home on April 14, 2012, I closely followed the Clinic’s physiotherapy program. Since then I have been working out at levels I had been told by my doctors here in the states would not be possible again. When exercising before I had stem cell therapy, I always had to be careful not to overdo it because I would get a sickness that sometimes lasted 2 days, completely wiping me out. This even occurred after the first liberation therapy, but no more. I’ve been working myself silly and have not yet felt sick. Real strength has returned and muscles have been popping out in places on my body where I haven’t seen them in many years. As of this writing today, and for about the last two weeks my right hand has been functioning normally in every respect. I’m not saying it has improved some, I’m saying it is now completely NORMAL! I can hardly believe it myself.

    Since I returned, and after only one month, the positive changes have been happening regularly and most every day. Most significantly, I think, my incontinence has completely improved and I am now able to almost totally control my urinary and elimination functions. All other disabilities aside, I think that this is one of the most important deficits that anyone with MS wishes they could get back! Incontinence is so embarrassing and not having control of that particular function somehow makes you feel lesser as a person. So I’m very happy to see the improvements there. My speech is back to normal. Although I never slurred my words, the thought process was oh-so-slow. Now my words come so quickly that I sometimes find myself stumbling over them…trying to say too much at once. I can’t complain about that!

    I am convinced that CCSVI Clinic is on to important discoveries about MS. They have figured this out and are doing the sequence of therapies correctly and the addition of the stem cells completes the need to repair the nerve damage that’s been done by the disease. In retrospect what they are doing suddenly makes complete sense to me. It’s still early yet and I guess time will tell to what extent my motor functions will come back, but if the last month is any indication, it could be everything, which excites me so much. I don’t know if that’s too much to hope for, but it’s the first time in 10 years that I’ve even really allowed the thought to cross my mind. The first fleeting thoughts of this after the original liberation therapy 2 years ago weren’t realistic. The good changes didn’t last. And consider this; a few months ago, I was in a wheelchair, in a permanent brain fog losing more of my independence and quality of life on a daily basis. All I had to look forward to was a deteriorating condition where others would have to take care of my every bodily function. Now I can’t wait to wake up every morning to check myself out. If anything I’m too impatient and working out too hard. But at least I can! Given my current state of health and ability to live and function on my own, the thing that is very certain is that I have a much better quality of life back and that wouldn’t have even been possible if it hadn’t been for the lucky discovery of CCSVI Clinic through an Internet search. My family and I will be eternally grateful for what has happened no matter how this turns out. Thanks to Dr. Gupte, the other doctors, the medical team and staff at the Clinic who made this all happen for me, I’m looking forward to each day with new health and optimism! May God Bless them all!

    I have a long way to go, but as long as my jugular veins are wide open and the stem cells continue to clean up the mess those narrowed veins left behind, and damaged nerves continue to regenerate, I believe the sky is truly the limit! My main focus at this point is not only to rebuild muscle but to get my legs to work together, which will restore my balance.

    Every day is a new gift that allows me more recovery. I can hardly wait for each morning to see the next improvement! There’s so much more happening in my body than I’ve even mentioned in this writing but I hope I’ve related the main message here…MS was my previous diagnosis.

    I will be starting a blog on my progress in a week or two if anyone wants to contact me or follow my improvement. I’m sure there are many of you out there who are skeptical or would want to know how this is going for me. I’ll post the site information back here once I have it up.The first fleeting thoughts of this after the original liberation therapy 2 years ago weren’t realistic. The good changes didn’t last. And consider this; a few months ago, I was in a wheelchair, in a permanent brain fog losing more of my independence and quality of life on a daily basis. All I had to look forward to was a deteriorating condition where others would have to take care of my every bodily function. Now I can’t wait to wake up every morning to check myself out. If anything I’m too impatient and working out too hard. But at least I can! Given my current state of health and ability to live and function on my own, the thing that is very certain is that I have a much better quality of life back and that wouldn’t have even been possible if it hadn’t been for the lucky discovery of CCSVI Clinic through an Internet search. My family and I will be eternally grateful for what has happened no matter how this turns out. Thanks to Dr. Gupte, the other doctors, the medical team and staff at the Clinic who made this all happen for me, I’m looking forward to each day with new health and optimism! May God Bless them all!

    I have a long way to go, but as long as my jugular veins are wide open and the stem cells continue to clean up the mess those narrowed veins left behind, and damaged nerves continue to regenerate, I believe the sky is truly the limit! My main focus at this point is not only to rebuild muscle but to get my legs to work together, which will restore my balance.

    Every day is a new gift that allows me more recovery. I can hardly wait for each morning to see the next improvement! There’s so much more happening in my body than I’ve even mentioned in this writing but I hope I’ve related the main message here…MS was my previous diagnosis.

    I will be starting a blog on my progress in a week or two if anyone wants to contact me or follow my improvement. I’m sure there are many of you out there who are skeptical or would want to know how this is going for me. I’ll post the site information back here once I have it up.For more information visit our site http://davidsmsstemcelljourney.blogspot.in/

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