Respiratory Decline; Duchenne muscular dystrophy occurs in boys and is characterized by progressive muscle degeneration and weakness leading to a decline in respiratory function. Strategies to arrest this severe progressive deterioration are needed to extend lives and improve quality of life. Results of three clinical trials using eteplirsen, an exon-skipping antisense oligonucleotide, show promising results, according to a study published in the Journal of Neuromuscular Diseases.
Muscular dystrophy is a group of genetic disorders that results in increasing weakening and breakdown of skeletal muscles. Near absence of dystrophin, a critical protein, results in inflammation, necrosis, and eventual replacement of functional muscle tissue with fibrosis and fat. Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy in boys that has a predictable disease course.
Respiratory decline in patients
Muscle weakness usually begins around the age of four in the thighs and pelvis follow by the arms. Most patients are unable to walk by the age of 12. Natural history data show that respiratory function declines linearly; also predictably in the second decade of life. Respiratory decline in glucocorticoid treat DMD patients is typically 5% annually in patients aged 10 to 18 years. Patients require increasing levels of clinical intervention as the disease progresses.
Investigators led by Navid Z. Khan, Ph.D., Senior Director, Global Medical Affairs, Sarepta Therapeutics, Inc., Cambridge, MA, USA, evaluate respiratory function in eteplirsen-treat patients; so from three clinical trials and compare them to patients match by age range, steroid use, and genotype from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) global database.
The three CINRG DNHS cohorts included: glucocorticoid-treat patients amenable to exon 51 skipping (20 patients), all glucocorticoid-treat CINRG patients (172 patients), and all glucocorticoid-treat genotype CINRG DNHS patients (148 patients). Approximately 13% of cases of DMD are amenable to exon 51 skipping therapies.
Experience respiratory decline
Patients in the global patient database experience respiratory decline; hence at rates in line with the well establish natural history of DMD. In contrast, the respiratory decline in patients treat with eteplirsen was significantly lower; also this was true across all stages of the disease evaluate. Specifically, both ambulatory and non-ambulatory patients demonstrate a slower rate of respiratory decline.
As the disease progresses, patients require increasing levels of clinical intervention; so including cough assist and ventilation support, and patients are at increase risk of death; so once this respiratory decline reaches a critical threshold. This work demonstrates that eteplirsen may slow the rate of respiratory decline; also therefore may delay time to milestones of decline.
This may have notable positive implications on quality of life; also because pulmonary decline is link to mortality; so slowing of decline may result in delay mortality. The investigators acknowledge that longer term follow-up is need. Eteplirsen is an antisense oligonucleotide approve by the FDA for the treatment; hence of Duchenne muscular dystrophy (DMD) in patients who have a confirm mutation of the DMD gene that is amenable to exon 51 skipping.