"Cost" of muscle wasting
Personal costs. It is often difficult to comprehend the devastating impact of skeletal and cardiac muscle wasting due to its indirect association with other primary causes of disease. Nevertheless, the following statistics are sobering.
- Muscle wasting occurs in ~ 80% of advanced cancer patients causing 35-50% of mortalities depending on the cancer type
- Over 50% of people over 80 suffer from sarcopenia, the age-related loss of muscle
- Heart failure occurs in 23 million people globally and also causes muscle wasting
- 24% of Iraq and Afghanistan war evacuations resulted from non-combat musculoskeletal injuries versus only 14% from combat injuries
- Prevalence of the most common muscular dystrophy is 1 in every 7250 males aged 5-24
Financial costs. The market potential for treating muscle wasting is enormous. Current costs exceed $550 billion, $93 billion for cancer alone, yet nothing can actually restore muscle mass or strength. Treatments primarily focus on increasing appetite, but fail to deter muscle wasting while corticosteroids can even hasten muscle degeneration. Thus, AVGN7 has the potential to revolutionize the clinical treatment of many different disease states, whether used alone or in combination with other therapeutics.
Limb-girdle muscular dystrophy (LGMD)2i
Most muscular dystrophies are caused by abnormalities in the dystrophin-glycoprotein complex ("DGC", see Pipeline for more information). This is true of Duchenne/Becker muscular dystrophy, which results from mutations in dystrophin, and in the dystroglycanopathies. These latter forms arise from aberrant glycosylation of DGC proteins and a compromised linkage to the extracellular matrix that ultimately induces muscle degeneration. Mutations in Fukutin-related protein (FKRP) produce a variety of dystroglycanopathies including LGMD2i or the more severe congenital muscular dystrophy type 1C (MDC1C).
Several studies of the P448L mouse, an animal model that harbors an FKRP mutation, have identified pathologies in muscle structure and function that resemble those occurring in LGMD2i patients. These include impaired strength, cardiac function and even gait abnormalities that resemble the Trendelenburg gait (see video). Replacing FKRP with AVGNF stabilizes skeletal and cardiac muscle structure in P448L mice and in turn, improves the function of both tissues and increases strength (see graph). It also improves exercise capacity in these mice.
Climbing out of the degenerative hole
Gene therapeutics capable of restoring the DGC by, in essence, replacing a mutated gene with a functional gene show incredible promise. Additional studies further suggest that their efficacy could be substantially improved with compensatory treatments that enhance muscle mass and strength like AVGN7. To learn more about our combinatorial approach and about different muscle wasting disease indications, click the link to the right.