Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy or DMD is the most abundant genetic neuromuscular disease in childhood. As it is an x-chromosomal recessive hereditary disease, it affects mainly boys. DMD belongs to the rare diseases, it affects one in 3,500 to 5,000 males born worldwide.
From early childhood on, DMD patients suffer from muscle weakness and muscle wasting. The motoric development, sometimes even the general development, is retarded and most of the boys never learn to run or to jump. With the disease progressing, patients become dependent on walking supports and wheelchairs between the age of 6 and 13 years, later artificial respiration is required. Most patients die of heart failure or respiratory insufficiency in their young adulthood.
DMD is caused by a mutation in the gene coding for the protein dystrophin. Dystrophin is essential for muscle cells: it stabilizes the membrane of muscle cells and protects the cells during muscle activities. Without dystrophin, normal activity causes excessive damage to the muscle cells, leads to inflammation and muscle degeneration. Over time, the muscle tissue is replaced by fat- and fibrotic tissue.
In some patients the defective part of the dystrophin RNA can be excised by using antisense technologies, a procedure known as exon skipping. The result is a shortened but still functional dystrophin. This process of building a shorter but still functional dystrophin also occurs naturally in a disease called Becker Dystrophy. Here, the course of the disease is much milder and slower compared to DMD, and most patients can lead a mostly normal life with a usual life expectancy.
UgimersTM have proven to induce exon skipping in a disease-relevant mouse model.
As the genes coding for dystrophin differ in human and mouse, UgimersTM for the human dystrophin gene are currently under development.