Anti-hypertensive drug may help slow progress of Duchenne muscular dystrophy

Dr Harry Dietz and his colleagues at Johns Hopkins University School of Medicine have published a paper in the prestigious scientific journal Nature Medicine which shows that a drug called losartan slows the progress of muscle degeneration in mdx mice - a model of Duchenne muscular dystrophy.

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Anti-hypertensive drug may help slow progress of Duchenne muscular dystrophy

Duchenne muscular dystrophy is an inherited disease characterised by severe muscle wasting. It occurs in 1 out of every 3,500 newborn boys. The first symptoms tend to appear between the ages of 3 to 5 and by the age of 11 most of the boys are wheelchair bound. The disease can limit life expectancy when individuals get into their late teens and early twenties. Duchenne muscular dystrophy is caused by a genetic mutation that results in the absence of the functional form of a muscle protein called dystrophin.

In healthy individuals, muscle is repaired by a type of stem cell called satellite cells. Following injury, the satellite cells become activated; they start multiplying and eventually develop into functional muscle cells. Duchenne muscular dystrophy is characterised by progressive muscle weakness and degeneration, a process that initially is compensated by an increased activity of the satellite cells. However this mechanism of muscle regeneration eventually appears to fail and the muscles can no longer repair themselves.

Previous studies suggested that muscle regeneration could be impaired by TGF-beta, a protein which is naturally present in muscle cells. Dr Dietz and his group investigated whether this is relevant to the muscle degeneration observed in Duchenne muscular dystrophy, by studying an animal model of the disease - the mdx mouse. The results of their experiments showed for the first time that mdx mice have increased TGF-beta activity in their muscles and that this indeed impedes satellite cells to develop into functional muscle cells. Therefore they decided to inhibit the activity of this protein to see if it had any effect on muscle repair.

Losartan, a drug commonly used to treat high blood pressure, has been shown to inhibit TGF-beta activity in other diseases. When the drug was given to mdx mice they showed significant improvement in their muscle regeneration when compared with untreated mdx mice. Dr Dietz and his colleagues then went on to study the effect of long term losartan treatment on the mdx mice. The mice were treated for 6-9 months with the drug and, compared with untreated mdx mice, showed significant slowing of disease progression in various muscle groups, including the ones most severely affected by the disease in the mouse. At 6 months of treatment the mice also showed an increase in muscle strength compared to the untreated mdx mice.

Although Losartan does not represent a cure by restoring dystrophin expression or by eliminating the degenerative process in the muscle it might prolong the ability of the muscle to regenerate and therefore to keep pace with the destruction that is taking place in the dystrophic muscle. The results of Dr Dietz’s research is a great step forward in finding treatments that might have the potential to slow the progression of Duchenne muscular dystrophy prolonging life and improving quality of life for individuals affected by the condition. In addition, Losartan treatment might also be beneficial for other forms of inherited or acquired muscle conditions. The experiments, however, have been carried out in animals and there is still a long way to go, before we know if this approach will work in humans and therefore could develop into an effective treatment.


Further Information and Links

Duchenne muscular dystrophy
For more information about this condition, go to our information pages.

Nature Medicine
The paper referred to in the above article was published in the journal Nature Medicine. Nature Medicine is subscription only so the original article is not freely available. The article itself is written in medically technical language with no summary in layman's terms.