Heart Failure Drugs Preserve Muscle in Muscular Dystrophy

What about this, any comments?

Both of them are apporoved drugs, farmacological approach and near treatment?

Am I missing something or this could be very promissing ...at least?

 

http://medicalcenter.osu.edu/mediaroom/releases/Pages/Heart-Failure-Drugs-for-MD.aspx

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Did PPMD get a committment about when results of Dr. Rafael-Fortney's research will be available?

PPMD has provided support for this combination study in the mdx mouse. (lisinopril and aldactone).   There is also a clinical trial in the planning stages.  We believe cardioprotection is essential and combination therapies will be required.  Many of the therapies (exon skipping. ataluren, myostatin inhibition)  in trial and/or in development, suggested to improve (or protect) skeletal muscle function and have little or no impact on the heart.  For this reason, understanding stain data from cardiac MRI is an essential step in the process as well as testing currently approved heart failure drugs and  combination of drugs such as ace inhibitors (lisiinopril)  and arb (losartin), ace and aldactone to protect and preserve heart function.  Some physicians are recommending inteventions at a certain age, the start of steroids and /or when they see changes on the echocardiogram.  The lack of consistent guidelines across the commnity is frustrating and frightening for families.   We are urging physicians to update current guidelines to include aggressive, preventative cardiac care.   Current studies and trials provide additional evidence for protecting heart function. 

Thats helpful information Pat, and I appreciate your participation. I'm looking for a direct response to my last post.

Clearly nothing with respect to a phase 1 clinical trial for these drugs will happen without results from this latest MDX mouse study by Dr. Rafael-Fortney. When can we expect those results, even if preliminary?

We have so little time, months even weeks mean a lot. We know any approximate date provided is a guess at best.

I don't mean to be rude. But we are on that tight-wire trying to decide if any "conventional" drug development process will ever come through for my boy. While the range of options has exploded in recent years, for those not in the "hot zone" for exon-skipping, there still remains no options on the immediate horizon.

We are running out of time. If something doesn't happen soon we will be one of those headed to Central America, or India, or god-knows-where searching from something absurdly risky, but  perhaps less risky than sitting here and waiting for more docs to finish with their mice.

 

 

David, mouse results are expected in about six months.  We need to know if we can use just one of those drugs or if we need them both together to be able to design the trial.  If we don't do the trial correctly and miss a positive result than everything gets set back.  Those are the issues we try to balance with speed--we don't don't want to take shortcuts that cause us more time later or worse, throw out a potentially useful therapy.

 

Sharon

I mean no disrespect. We all appreciate the hard work, and I too am in the scientific field so I know all the steps must be taken.

But I remember hearing similar statements about Idebenone in 2005, utrophin upreg in 2007, ACE-031 in 2010 ... and yet the only significant progress towards phase 3 I can see in 2011 is with exon-skipping. I'm overjoyed for those families in the "hot zone." It's just not us.

 

David, keep in mind that what's "hot" therapeutically can change quickly and there's a pretty full next generation pipeline behind the things that are in clinical testing now.  Unfortunately the rate of success for new drugs is pretty low across the board in all fields.  We have spent some time studying the kinds of things that contribute to the high failure rate and the long time lines to see if we can spend dollars strategically to change that for DMD.  We think it's important to identify and fund specific promising therapeutics, but we are also trying to influence the whole process in our favor.  You can find some of this landscape analysis on the PPMD site at http://www.parentprojectmd.org/site/PageServer?pagename=Advance_ind... and the implementation plan at http://www.parentprojectmd.org/site/PageServer?pagename=Advance_fun...

 

Sharon


Hi Juan

 

I am relatively new to  PPMD site, just joined 4 weeks ago  , but have been associated with DMD since my son Khush was diagonised with DMD when he was 18 mts old . Now he is 4 yrs 5 mts old . His missing exons are 52 to 54 , so he is eligible for exon skipping 55 , which is long way down the line .

 

Recently I came across two articles one abt Losartan and other of combination of Lisinopril and Spironolactone . All these heart drugs do show some promise on  preserving skeletal muscles as well . Proof of concept is already established on DMD mice .

I fully agree with u and others that time for us is short and long for trials . These drugs are not something new and just taken off the shelf for trial on DMD mice  . They have been there since 1995 and some ace inhibitors are also used on diabetic patients who are at high risk to cardiac attacks,but no muscle damage  , so it should not be too long to apply these drugs in single or combo on our ambulatory kids .

 

In this regard I met my son's Neurologist last week 22nd sept 2011 and she too was excited on reading these articles . She has asked me to gether more information abt these drugs usage on DMD  and connect her to the researchers / doctors who have worked with these drugns on  DMD mice . I am on my path to do that . She would like to put a proper proposal before the Hiospital's IRB and then go ahead with the pilot study on young DMD kids .

In this respect can u let me know in detail abt yr meeting with yr son's pediatrician who knows something abt safe dosage in young DMD kids like four , five yrs old

 

Rgds Ambrish( From Mumbai - India  )

 

My email id is matex1884@gmail.com

 

Cell +91 9870304838

 

JUAN PEDRO ARBULU said:

David,

 

I know there is a preventive dose used for kids starting at 4 years, I talked to the pediatric cardiologist, she uses the combination as preventive with kids here in Lima with very low side effects, that is whta I was loking for , my appointment is tomorrow night , i´ll let you know what she tells me about it.

greetings

JP.

David said:

Juan - I did a bit of research and its still unclear to me how you would move on this independently of a clinical study that replicates the findings on the MDX mouse.

 

http://www.medicinenet.com/lisinopril/article.htm

 

For treatment after heart failure, lisinopril dosing recommendations stop after six weeks.

Treatment of heart attack (myocardial infarction) is started with individual doses of 5 mg followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg daily. Treatment is continued for 6 weeks.

 

For treatment of high blood pressure, lisinpril dosing is 20-40mg/day, with little improvement of higher doses

The starting dose of lisinopril for treating high blood pressure is 10 mg daily. The usual dose range is 20-40 mg daily. A dose of 80 mg is not much more effective than 40 mg.

 

Do you know how the dosage given to MDX mice would translate to humans? I didn't find that in the Circulation article, but most of that article is over my head anyway.

 

Dear Ambrish,

 

I have started about 2 months ago with lsisinopril and spirolactone, I will send you details about my conversation to your email.

JP.

Ambrish Kapadia said:


Hi Juan

 

I am relatively new to  PPMD site, just joined 4 weeks ago  , but have been associated with DMD since my son Khush was diagonised with DMD when he was 18 mts old . Now he is 4 yrs 5 mts old . His missing exons are 52 to 54 , so he is eligible for exon skipping 55 , which is long way down the line .

 

Recently I came across two articles one abt Losartan and other of combination of Lisinopril and Spironolactone . All these heart drugs do show some promise on  preserving skeletal muscles as well . Proof of concept is already established on DMD mice .

I fully agree with u and others that time for us is short and long for trials . These drugs are not something new and just taken off the shelf for trial on DMD mice  . They have been there since 1995 and some ace inhibitors are also used on diabetic patients who are at high risk to cardiac attacks,but no muscle damage  , so it should not be too long to apply these drugs in single or combo on our ambulatory kids .

 

In this regard I met my son's Neurologist last week 22nd sept 2011 and she too was excited on reading these articles . She has asked me to gether more information abt these drugs usage on DMD  and connect her to the researchers / doctors who have worked with these drugns on  DMD mice . I am on my path to do that . She would like to put a proper proposal before the Hiospital's IRB and then go ahead with the pilot study on young DMD kids .

In this respect can u let me know in detail abt yr meeting with yr son's pediatrician who knows something abt safe dosage in young DMD kids like four , five yrs old

 

Rgds Ambrish( From Mumbai - India  )

 

My email id is matex1884@gmail.com

 

Cell +91 9870304838

 

JUAN PEDRO ARBULU said:

David,

 

I know there is a preventive dose used for kids starting at 4 years, I talked to the pediatric cardiologist, she uses the combination as preventive with kids here in Lima with very low side effects, that is whta I was loking for , my appointment is tomorrow night , i´ll let you know what she tells me about it.

greetings

JP.

David said:

Juan - I did a bit of research and its still unclear to me how you would move on this independently of a clinical study that replicates the findings on the MDX mouse.

 

http://www.medicinenet.com/lisinopril/article.htm

 

For treatment after heart failure, lisinopril dosing recommendations stop after six weeks.

Treatment of heart attack (myocardial infarction) is started with individual doses of 5 mg followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg daily. Treatment is continued for 6 weeks.

 

For treatment of high blood pressure, lisinpril dosing is 20-40mg/day, with little improvement of higher doses

The starting dose of lisinopril for treating high blood pressure is 10 mg daily. The usual dose range is 20-40 mg daily. A dose of 80 mg is not much more effective than 40 mg.

 

Do you know how the dosage given to MDX mice would translate to humans? I didn't find that in the Circulation article, but most of that article is over my head anyway.

 

Hi,Juan

Hope you are well in Peru.How is the young man doing?I mailed you a request thro your yahoo mail yesterday,did you get it?Waiting anxiously to hear from you.Thanks and good gday.

Hello Wainanaina,

 

i will respond via email.

 

Seems promising but here in Scandinavia everything goes in slowmotion, if only this research could be shared with scientist in Europe maybe things will step up a notch. There must be a knowledge exchange in the search for answers against Duchenne, I have'nt heard of any collaboration like so.

Hi Juan

How is the year progressing for you and your little boy?I came across something interesting and kind of wondered whether other parents may have come across it too.The great enemy to the growth of the muscles is the fibrosis arising from the DMD condition afflicting our sons; i stand to be corrected on this one.There is this medical product Decorin for treatment of fibrosis that you can read on in the links below.Thanks and have a great day.

Using decorin, an anti-fibrosis agent, to improve muscle recovery after injury

http://www.skeletalmusclejournal.com/content/1/1/21


www.sportsinjurybulletin.com/archive/decorin.htm

Regards

Alex

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