Does anybody know why Proteasome Inhibition is not being discussed as widely as some other approaches for a potential DMD treatment/cure? See the following papers for details:

The studies were done on the mdx mouse and explants of human muscle tissue. Basically it allows the dystrophin that is being made by the gene to not be targeted for destruction by the body’s “quality control system”, it can then localize correctly, and even though it is truncated it can probably still perform a function to the body. It might not be a complete cure but it could transform the disease to a milder phenotype.

I ask this because it seems very promising and there is no mention of it in the 2008 Research Approaches paper which seems very comprehensive.

There is even one FDA approved proteasome inhibitor drug available now – Velcade (studied in the second paper above). It’s currently used for some cancer treatment.

My son doesn’t have DMD but he has LGMD 2D and a new paper just came out showing how Velcade rescues his misfolded alpha-sarcoglycan protein made by one of his two SGCA genes (the other misfolded alpha-sarcoglycan protein made by his second SGCA gene is rescued from degradation, but cannot localize to the muscle cell membrane due to the nature of its misfolding).

But as you can see from the DMD papers, it has the potential for doing a similar job in DMD – it rescues dystrophin, beta-dystroglycan, alpha-sarcoglycan---basically the whole DGC complex. The attached paper shows that it is mutation specific for DMD and BMD ---- the majority of proteins formed were rescued and localized however some were not.

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Just wanted to say that I e-mailed Dr. Gunter Scheuerbrandt about this a while back and he thanked me. Apparently he was unaware of these studies and said that he would look into it and include it in his periodic publications.

I was wondering if anybody has heard anything more about this? It seems promising because there is at least one proteasome inhibitor already approved in the U.S. and from what I gather from the papers it would be a medicinal treatment that actually works on restoring truncated dystrophin expression (by blocking the reputed degradation pathway), unlike steroids.
Thank you for posting this. Never hard of this before. Hope PPMD can look into this.

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