losartan use in LGMD

[Andy]

Hello ... hope everyone is well ....

just wondered on your opinion of the use of losartan on LGMD.

Is the drug safe to take if you have no blood pressure problems ?

take care

Andy

[David Feder]

Andy: when we start losartan in all situations (arterial hypertension; diabetes, cardiac dysfunction) we must start with low dose and increase slowly. If you give high dose than necessary the blood pressure go down and it's possible to present renal problem. This medication must be used under medical supervision.
David

[Mirek]

Hello David,
if I remember well there was planned clinical trial with another TGF-beta blocker - Tamoxifen in Brazil.
Have it passed? What was the result?
Mirek

[David Feder]

Hi Mirek:
Thank you for this question. You make me remember that we both discuss TGF beta 1 since 2004 when there was few articles about TGF beta 1 in DMD. Now there are several possibilities in study to block TGF beta 1. For example: antibody anti TGF beta 1, losartan and others; histone desacetylase inhibitor can block TGF beta 1 too (Trichostatin A, a histone deacetylase inhibitor, suppresses collagen synthesis and prevents TGF-beta(1)-induced fibrogenesis in skin fibroblasts.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12169274&query_hl=4&itool=pubmed_docsum )

I start with tamoxifen because the drug can act in TGF beta 1. Until this moment I can prove that in my mdx mice the drug block TGF beta 1. I give the muscles to a researcher that promise to make free this measures in PCR - real time and until this moment she don’t give me the results. Now I look for another team to make this measures. This is the first step to start a human trial.
David

[mirek]

antibody anti TGF beta 1, losartan, tamoxifen, histone desacetylase inhibitor ...
Where can we expect the lowest side effects?
Antibody anti TGF beta 1?

[David Feder]

Mirek: I have no certainty but I think that anti-TGF beta 1 can give less side effects. The side effects is not my first preocupation. I have other questions:
1) Each drug will be tested first?
2) Block TGF beta 1 can give results in all ages?
3) Wich associations with TGF beta 1 blockers is more effective: steroids, antioxidants, creatinem vitamins, and others. I think that in DMD we must try thingytail of treatments and not each drug alone.
David

[Mirek]

And what about UDCA? It blocks apoptosis induced by TGF-beta1, slightly upregulates utrophin, no side effects...

[David Feder]

UDCA too.
But I see an problem in mdx mice studies. The researchers don't have a model to study mdx mice. For example the last article that I post about alpha lipopic acid they study the mice only for 10 days. In general the researchers study the effect less than 30 days. The only drug studied 1 year in mdx mice was HCT 1026 (nitroflurbiprofen).
David

[ahmed]

hi:

[hb]

David, the article does not mention about any side effect.. nor has any mention regarding regarding implications on Muscular dystrophy with High or normal Blood pressure ...

Now, I would like to know, if a person who is MD and has normal BP can try this for improving the situation as mentioned??? ....

Also, secondly, for those who have higher BP, will it only lower the BP to normal and will add to the recovery process??? your comment..
Hemant

[David Feder]

Hemant: Losartan is a safe medication without any serious side effect.
To people with High pressure - the dose that reduce and control the blood pressure.
To people with normal pressure - the dose that don't reduce significantly the blood pressure. The doctor start with low dose and increase slowly.
David