In the fall of 2009, I emailed one of the researchers at Johns Hopkins who was looking into Losartan, and he informed me that he thought a DMD trial for Losartan was expected to begin in 2010. However, I have not heard anything in response to some further email inquiries I've sent. Does anyone else have any information?

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Dr. Chris Spurney, cardiologist at CNMC in Washington, DC is suppose to run the losartan trial at CNMC. He may be coordinating all efforts with the Hopkins team. Atleast this is my understanding from a recent meeting I attended. I have no idea when this trial will launch off the ground. My son is taking 50mg at bedtime and tolertaing the drug without experiencing any adverse side effects thus far. He was started on the drug in July 2009. I handed Dr. Leshner, our son's neurologist at CNMC, several articles re: the losartan's effects in muscle in mdx models and then dog models. He finally consented to writing the prescription for the drug. At first, our son was prescribed 12.5mg daily then the dosage was slowly increased to where he is now, at 50mg daily. Feel free to inbox me if you are interested in receiving the articles. I can email them to you.
Tina,

I'm also very interested in reading the articles on Losartan, if you don't mind sending them. What's the best way?

Thanks!

Tonya
Thank you, Tina. Have you seen any effects for Mark, and about how much does he way? I can't tell how old old he is in his picture, but Alex is 11, and is really starting to have difficulty getting around. He uses his scooter most of the time outside of the house, and scares the daylights out of me as he wobbles around the rest of the time. I'm trying to buy some time so that when better treatments emerge there's something left to treat. Lastly, I believe that there are numerical models for predicting how much medication in a human being would be required to replicate the effect of that medication in a mouse or a dog, do you know where Mark's dose fits on that range?
(Unpublished data, 2009) The effect of losartan in the skeletal muscle morphology of Golden Retriever Muscular Dystrophy: a promising drug for dystrophic muscle regeneration? *

Marina Brito da Silva - research conducted to get the Master of Science in Department of Surgery of the Sao Paulo University, Faculty of Veterinary Medicine and Animal Science, Sao Paulo, SP, Brazil under orientation of Maria Angelica Miglino.

Duchenne Muscular Dystrophy (DMD) has the substitution of the muscle by connective tissue as its most relevant characteristic. Once fibrotic proliferation is a major obstacle to the efficacy of therapy for muscular dystrophies, early interventions to prevent it will probably be necessary as part of an effective treatment. A significant correlation between fibrosis and the expression of TGF-beta 1, a multifunctional cytokine, in Duchenne muscular Dystrophy has been reported, emphasizing the role of cytokine in the development of muscle fibrosis, and suggesting it as target for fibrosis therapies. In this study we evaluated the effect of losartan over the development of connective tissue on the skeletal musculature of the canine model GRMD. One dystrophic dog was previously used in the pilot study to estipulate the dosage and side effects caused by losartan. Five dystrophic dogs, two male and two female and one control animal were used in the experiment. A dose of 50mg of losartan was orally given once a day. The clinical and laboratorial exams did not show any adverse effect through the experimental period. Therefore losartan utilization showed to be safe therapy. Muscle biopsy fragments have been removed before starting losartan (T0) and after (Tf) were used for histology and TGF beta-1 imunohistochemistry to compare this two times. The evaluations range of motion and limb circunference measures within imunohistochemistry and collagen quantification results helped to infer about losartan effect in the dystrophyc muscle fibrosis. Range of motion and limb circumference values did not show statistical difference. Although the percentage of connective tissue deposition area in the animals in Tf was statistically lower lower than T0. The decrease of TGF beta-1 signalization showed in imunohystochimestry pictures within the decrease of connective tissue deposition, after losartan, suggest an inhibitory effect of this medication through this cytokine in the studied GRMD muscle.

* NOTE: the dogs were treated for 2 months on average.
This is very promising..so it reduces fibrosis but does not increase strength (which is expected) in dogs. Will they start the trial this year? Do you know Tina?


Tina said:
(Unpublished data, 2009) The effect of losartan in the skeletal muscle morphology of Golden Retriever Muscular Dystrophy: a promising drug for dystrophic muscle regeneration? *

Marina Brito da Silva - research conducted to get the Master of Science in Department of Surgery of the Sao Paulo University, Faculty of Veterinary Medicine and Animal Science, Sao Paulo, SP, Brazil under orientation of Maria Angelica Miglino.

Duchenne Muscular Dystrophy (DMD) has the substitution of the muscle by connective tissue as its most relevant characteristic. Once fibrotic proliferation is a major obstacle to the efficacy of therapy for muscular dystrophies, early interventions to prevent it will probably be necessary as part of an effective treatment. A significant correlation between fibrosis and the expression of TGF-beta 1, a multifunctional cytokine, in Duchenne muscular Dystrophy has been reported, emphasizing the role of cytokine in the development of muscle fibrosis, and suggesting it as target for fibrosis therapies. In this study we evaluated the effect of losartan over the development of connective tissue on the skeletal musculature of the canine model GRMD. One dystrophic dog was previously used in the pilot study to estipulate the dosage and side effects caused by losartan. Five dystrophic dogs, two male and two female and one control animal were used in the experiment. A dose of 50mg of losartan was orally given once a day. The clinical and laboratorial exams did not show any adverse effect through the experimental period. Therefore losartan utilization showed to be safe therapy. Muscle biopsy fragments have been removed before starting losartan (T0) and after (Tf) were used for histology and TGF beta-1 imunohistochemistry to compare this two times. The evaluations range of motion and limb circunference measures within imunohistochemistry and collagen quantification results helped to infer about losartan effect in the dystrophyc muscle fibrosis. Range of motion and limb circumference values did not show statistical difference. Although the percentage of connective tissue deposition area in the animals in Tf was statistically lower lower than T0. The decrease of TGF beta-1 signalization showed in imunohystochimestry pictures within the decrease of connective tissue deposition, after losartan, suggest an inhibitory effect of this medication through this cytokine in the studied GRMD muscle.

* NOTE: the dogs were treated for 2 months on average.
My son will be 9 this month. He weighs around 67 pounds.
Good questions Paul.
Some background info first. Up until May 2009, our son was taking 18mg of deflazacort daily, which equates to 12.5mg of prednisone daily. He was on this dose since diagnosis at 3 1/2 years old. According to the numbers, going by weight, his dose should have been increased but it was never increased because his strength scores have been maintained. So, in May 2009, for reasons I can discuss later if you are interested in hearing, I decided to decrease his steroid dose to 18mg every other day. I decided to do this just as a trial over the summer of 2009. In the meantime, he started taking losartan in July 2009. He returned to school in late August and since I didn't notice any muscle strength weakness, I decided to keep him on the every other day steroid regimen. So, essentially, according to their guidlines, he is really at a subtherapeutic dose, right? He's been taking losartan for 6 months now and has been on the ADT ( Alternate Day Therapy) regimen for 8 months. His strength is still the same but I do notice on some evenings he tires more going up the stairs. But, his condition has not deteriorated enough to encourage me to put him back on the daily regimen dose. Once, I witness this, I plan on doing so.
One more thing, his vitamin d levels inspite of taking 2,200 iu's of vitamin d daily remain at a subtherapeutic level. So, 2 months ago we started him on a high vitamin d regimen. This was the advice Dr. Leshner received from an endocrinologist. He's been getting 50,000 iu's weekly for 6 weeks then he converts to 50,000 every other week with follow up blood work to check on his levels coming soon.
I know this information doesn't give you a definitive answer as to whether or not losartan is helping because truly I don't know if the losartan has made a difference but wanted to be completely honest in telling you everything about his changes that have been made so you can form your own decison. I am certainly not encouraging anyone to change their son's steroid regimen or decrease his dose. I initiated this on my own without discussing it with his neurologist first and thankfully, he responded fine to the changes.
It is my understanding and I have no literature to provide for you that the dose from the mice in the losartan trial to boy would equate to 100mg/daily. Again, you are talking about mice and kids processing things differently and showing toxicity differently. I would never bump my kid up to 100mg daily without consulting the specialist team, first. I think the highest dose prescribed for kids with various diagnosis has only been 50mg daily.

I hope this helps.

Take care, Tina
Our son currently has no cardiac issues so if anything else, the losartan was prescribed prophylactically for the heart. It would be great if if provided better muscle strength or just maintained his strength for the rest of his life but I'll take fibrosis reduction, if that is the result of the drug.

I left the meeting not knowing anything about a trial date but got the impression the goal was to start it 2010 or 2011. Sorry, I just don't have that specific info which is why I pushed for it back in July. But, everybody has their own opinions when it comes to giving their child a drug without knowing the results from studies first and I respect that.
Tina,


Thanks again. I wouldn't expect to see strength gain, and frankly I don't really expect to see it in any of the treatments being tested now. At this point I'm looking to slow in the rate of decline to push out Alex' remaining life expectancy, going off his feet, losing the ability to care for and feed himself, etc. He'll probably be off his feet by the end of this year at the rate I see him declining. It does not appear that the student had much of a placebo arm to her study, so you can't really compare the extent of the performance decline between placebo and treatment groups
Tina said:
Dr. Chris Spurney, cardiologist at CNMC in Washington, DC is suppose to run the losartan trial at CNMC. He may be coordinating all efforts with the Hopkins team. Atleast this is my understanding from a recent meeting I attended. I have no idea when this trial will launch off the ground. My son is taking 50mg at bedtime and tolertaing the drug without experiencing any adverse side effects thus far. He was started on the drug in July 2009. I handed Dr. Leshner, our son's neurologist at CNMC, several articles re: the losartan's effects in muscle in mdx models and then dog models. He finally consented to writing the prescription for the drug. At first, our son was prescribed 12.5mg daily then the dosage was slowly increased to where he is now, at 50mg daily. Feel free to inbox me if you are interested in receiving the articles. I can email them to you.
I don't know when the group at Hopkins is planning to start their Losartan trial, but there's another one already underway:

ACE Inhibitor vs. Losartan

Five centers are collaborating in a double-blind randomized study to determine if the ACE inhibitor lisinopril is more effective than losartan in treating heart function in Duchenne. Investigators will also determine if the participants who receive losartan show any improvements in muscle strength. The study will be recruiting 150 boys and men of all ages with a positive diagnosis of Duchenne. Participants must show less than 5% normal levels of dystrophin in their muscles and also have cardiac ejection fractions below 50%. Participating centers include Nationwide Children’s Hospital in Columbus, Boston Children’s, St. Louis Children’s, University of Minnesota and UC Davis. The study is recruiting now.

I will try to find out where you can inquire about participation and a blurb about this study will also appear in the upcoming PPMD newsletter. This study was funded by MDA.

Sharon
Jerry Mendell's team in Columbus is working on this. You can email his research coordinator for more details.
Paul, you can certainly ask Flanigan since he is now part of that team.

Sharon Hesterlee said:
I don't know when the group at Hopkins is planning to start their Losartan trial, but there's another one already underway:

ACE Inhibitor vs. Losartan

Five centers are collaborating in a double-blind randomized study to determine if the ACE inhibitor lisinopril is more effective than losartan in treating heart function in Duchenne. Investigators will also determine if the participants who receive losartan show any improvements in muscle strength. The study will be recruiting 150 boys and men of all ages with a positive diagnosis of Duchenne. Participants must show less than 5% normal levels of dystrophin in their muscles and also have cardiac ejection fractions below 50%. Participating centers include Nationwide Children’s Hospital in Columbus, Boston Children’s, St. Louis Children’s, University of Minnesota and UC Davis. The study is recruiting now.

I will try to find out where you can inquire about participation and a blurb about this study will also appear in the upcoming PPMD newsletter. This study was funded by MDA.

Sharon
Thanks Ofelia and Tina. I think we see Dr. Flanigan again in June. I'll check with him then.

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