Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene
Muscular dystrophies are a group of genetic disorders which cause muscle weakness and progressive disability. Duchenne muscular dystrophy is the most common and progresses most rapidly. It is caused by the presence of certain defects (called nonsense mutations) on the X-chromosome in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. The mutation prematurely stops the production of a normal dystrophin protein, leading to a shortened dystrophin protein that does not function properly. These changes cause muscle fragility that progressively leads to weakness and loss of walking ability during childhood and adolescence. Boys only have one X chromosome, and thus one single copy of the dystrophin gene, hence they have a much higher probability of developing Duchenne muscular dystrophy than girls. A very small number of girls develop Duchenne muscular dystrophy if they inherit two mutated Xchromosomes, one from each of their parents.
Duchenne muscular dystrophy usually presents between the ages of 1 and 3 years and affected children may appear weaker than other children, and have difficulty walking, standing, or climbing stairs, and may have behavioural or learning difficulties. After the age of 12 most children will need to use a wheelchair. During adolescence, breathing muscles can weaken, causing shallow breathing and a less effective cough mechanism, which can lead to chest infections. Weakness of the heart muscle, called cardiomyopathy, occurs in almost all patients by the age 18. The life expectancy of people with Duchenne muscular dystrophy depends on how quickly and intensely muscle weakness progresses and on how it affects the patient’s ability to breathe. The average lifespan is less than 30 years.