Friday 20 July 2012
Potential new treatment for Duchenne muscular dystrophy discovered
Scientists based in the USA have discovered that a drug-like molecule, called RTC13, may have the potential to treat the nonsense mutations which cause ten - fifteen percent of cases of Duchenne muscular dystrophy. Using a mouse model of Duchenne muscular dystrophy, they found that treating mice with the potential drug restored dystrophin production in a range of muscles including the heart and breathing muscle (diaphragm).
Nonsense mutations are responsible for causing between ten and fifteen percent of Duchenne muscular dystrophy cases. A nonsense mutation is when one letter of the DNA blueprint is changed to another letter - like a spelling mistake - to make a signal which stops our cells reading the rest of the blueprint. Previous research has shown that certain chemicals, such as ataluren, can encourage cells to ignore this stop signal and carry on reading to the end of the DNA blueprint. Scientists from the University of California, Los Angeles used high-throughput screening - a technology which tests the properties of many potential drugs very quickly - to search for other chemicals which can help cells to read through stop signals and found a promising candidate named RTC13.
RTC13 was tested for its ability to restore dystrophin expression in model systems of Duchenne muscular dystrophy. Initial work using Duchenne muscular dystrophy cells grown in the laboratory showed that RTC13 restored dystrophin levels at least as well as ataluren - a potential therapy currently in clinical trial for Duchenne and Becker muscular dystrophy. The researchers then examined the effects of RTC13 in mdx mice (a mouse model of Duchenne muscular dystrophy) and found that injection of RTC13 directly into the muscles generated muscle fibres with increased levels of dystrophin, whilst injection of the drug into the abdomen restored dystrophin expression in a range of muscles including the legs, heart, and breathing muscle (diaphragm). The researchers also found that there was less muscle damage, and that mice treated with RTC13 performed better in strength tests than untreated mice.
The research showed that RTC13 may have the potential to restore dystrophin production in the muscles of boys with Duchenne muscular dystrophy who have a nonsense mutation. This could represent ten to fifteen percent of boys with the condition.
However, this work is at a very early stage in animal models and before the potential drug can be tested further, researchers intend to produce a form of RTC13 which can be taken orally. It will, therefore be some time before the potential drug will be ready to enter clinical trials.
Although clinical trials of a drug called ataluren are underway (it is also aimed at treating nonsense mutations in Duchenne and Becker muscular dystrophy), it is still a good idea to research other drugs that may have a similar effect. This allows researchers to find new drugs that may work better or have fewer side effects. Also, many drugs that go to clinical trial do not reach the market, so it is vital to have a constant stream of different potential drugs entering the process to provide the best chance of producing an effective treatment for patients in the future.
For more information about Duchenne muscular dystrophy
Read about the Duchenne muscular dystrophy research we are funding
Find out more about ataluren