DMD - Duchenne Muscular Dystrophy
DMD is an inheritable lethal childhood’s disease with an incidence of approximately 1 in 3 500 newborn boys (Emery AEH et al, 1991 and Emery AEH et al, 2003). In DMD, boys begin to show signs of muscle weakness as early as the age of 2 (Figure 1). The disease gradually weakens the skeletal or voluntary muscles in the arms, legs and trunk. Due to progressive muscle weakness, DMD patients are often wheelchair bound before the age of 12.
At a later stage, the boys’ respiratory muscles are also affected and slowly the boys drift into respiratory failure with a forced vital capacity (FVC) of less than 25%. The cardiac muscle is also affected and recent figures estimate that around 15% of DMD cases die of a primary cardiomyopathy. The mean age of death increased to around 25 – 30 years over the last years due to an improved standard of care and the recent introduction of assisted ventilation in the later stages of the disease.
Typical progression of clinical symptoms with age of Duchenne Muscular Dystrophy patients.
At present, there is no effective therapy for DMD available. In addition to surgical and physical therapeutic measures, glucocorticosteroids are used in DMD. Clinical studies with glucocorticosteroids have shown a prolongation of the ability to walk of approximately 2 years, albeit accompanied with (sometimes severe) side effects (Manzur AY et al, 2009). However glucocorticosteroids are not able to induce dystrophin-like proteins and therefore do not alter impact the fundamental cause of DMD. Other available treatment is mainly supportive, such as physiotherapy, wheelchair and other mechanical support (braces), scoliosis surgery, assisted ventilation and treatment of respiratory infections.
Our exon skipping technology is based on interference with exon inclusion signals during the splicing of the pre-mRNA, in order to induce the skipping of the targeted exon from the mature mRNA (messenger RNA) and to increase the level of functional transcripts.
Exon skipping is a highly specific technique. Therefore, it cannot be applied to all sub-populations of DMD patients. To know if exon skipping could potentially help, it is essential to…
Due to an improved standard of care, the life-expectancy of boys and young men with DMD has increased significantly over the last years. Standard of care considerations were published in the Lancet in two parts in 2010 (Bushby et al. Lancet Neurol 2010; 9 (1): 77-93 and Bushby et al. Lancet Neurol 2010; 9 (2): 177-189).
The lead product, drisapersen (PRO051/GSK2402968), is currently involved in several clinical studies. PRO044, which aims at a different sub-population of DMD patients, is in a Phase I/IIa clinical study and PRO045 and PRO053 are anticipated to enter the clinic in the first half of 2013.