Research News :- New drug :- a potential treatment for duchenne muscular dystrophy

New drug :-  a potential treatment for duchenne muscular dystrophy

Muscular dystrophy campaign

61 southwark street

London SE10HL 

5^th April 2012

An international group of scientists, led by prof Gordon lynch at the university of Melbourne, Australia, have shown that increasing the amount of protein called heat shock protein 72(Hsp72) can have a beneficial effect in a mouse model of DMD. Giving amice drug called BGP-15(BGP-15 increasing Hsp72) improve the function of the limb muscles and more importantly, the breathing muscle as well as increasing the lifespan of the mice. Further work will have to be done before it can be confirmed that this approach will be beneficial for boys with DMD.

What did this research show?

The lack of dystropin in DMD leads to a series of events that cause the muscle to weaken and waste. One these events is a large increase in the amount of calcium inside the muscle .small tears in the muscle membrane that arise due to the lack of dystropin allow calcium into the muscle from the outside environment. High levels of calcium are damaging and lead to chronic inflammation and breakdown of the muscle.

 

The researchers decided to investigate proteins that are known to help regulate the amount of calcium inside the muscle. They wanted to find out if controlling the amount  of calcium in the muscle could prevent muscle damage occurring. They focused on a protein called heat shock protein 72 (Hsp72) known to be able to help cells regulate their calcium level.

Prof  lynch and his team used mdx mice (the mouse model for DMD) that were specially bred to also produce high level of Hsp72 in their muscles. When compared to  mdx mice that produce normal level of Hsp72, these mice had less muscle breakdown, improved muscle strength and importantly less degeneration of the diaphragm (breathing muscle). The researcher showed that this was due to the fact that the muscle were being repaired more efficiently.  

 Since these initial results were promising, the team decided to test whether a drug,called BGP-15, that is known to increase levels of Hsp72 in humans might show similar results. BGP-15 is currently in clinical trial to treat diabetes. They looked at two mouse models of DMD-the mdx mouse and the very severely affected double knock out  (dko) mouse. Dko mice are missing not only the dystrophin protein, but also a related protein called utropien. Utrophin is known to be able to compensate for a lack of dystrophin and if both proteins are missing, symptoms in mice are more severe and are very like those seen in boys with DMD. BGP-15 treated mice had decreased muscle breakdown and greater muscle strength than untreated mice. They also had less degeneration in the diaphragm which points to an improvement in their ability to breathe as well as an increase in lifespan.

Prof Dame key Davies, a muscular dystrophy campaign grantee and one of the team who working on the project said;

It is exciting to see that increased levels of the protein Hsp72, boosted by a novel drug called BGP-15, extends the life of these mice substantially. This makes it much likely that this drug will benefit patients not only with DMD, but with other muscle disorders too.

Dr marita pohlschmidt, director of research at the muscular dystrophy campaign said;

 The result are encouraging news for the development of a treatment that could delay the progression of DMD and therefore could improve the live expectancy of the boys. In addition, the suggested drug could be used in conjunction with one of the promising potential therapies that are currently tested in clinical trial, should any of them show a clinical benefit.