AVGN7 is a gene therapeutic. It uses a non-pathogenic virus that cannot cause disease to introduce the smad7 gene into skeletal muscle and the heart. This gene ultimately produces a Smad7 protein, which blocks the actions of several muscle growth inhibitors including myostatin, activin and GDF-11. By "inhibiting the inhibitors", muscle protein synthesis is increased while muscle protein degradation is reduced. This in turn increases muscle mass and strength in healthy mice and can completely prevent the muscle wasting that occurs in mice with tumors. Furthermore, AVGN7 can restore muscle mass and strength in tumor-bearing mice well after significant muscle wasting has occurred, indicating that AVGN7 can also function as a prophylactic therapeutic.
AVGN7's actions aren't limited to skeletal muscle as it can also prevent the cancer-induced wasting of the heart or "cardiac cachexia" in mice. Several animal studies further indicate that attenuating myostatin induces physiological cardiac hypertrophy - the good kind - and enhances cardiac performance in a manner that resembles elite endurance athletes. Our animal studies further indicate that AVGN7 specifically targets skeletal and cardiac muscle with no evidence of off-target or deletarius effects. This is extremely important as very serious off-target effects have been reported with circulating "ligand-traps" for myostatin. In fact, AVGN7 was specifically designed to avoid such effects while still enhancing muscle mass and strength.
Because AVGN7 blocks intracellular pathways that are commonly activated with muscle wasting in general, it has the potential to broadly treat a wide variety of diseases and as a result, transform how muscle wasting is treated. It could even be used as a co-therapeutic, for example, with muscular dystrophy as several studies very clearly indicate that even replacing the mutated gene cannot fully restore muscle mass and strength to normal. Ancillary treatments are, therefore, needed to overcome the functional deficits resulting from years of muscle wasting and to ultimately restore muscle mass and strength.
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Over 70,000,000 people in the US, Europe and Asia/Pacific suffer from muscle wasting. Cancer cachexia, muscular dystrophies, age-related sarcopenia, heart failure, chronic kidney disease, COPD, musculoskeletal injuries and peripheral neuropathies are all associated with the progressive loss of muscle mass and strength commonly called "muscle wasting".
Personal costs. It is often difficult to comprehend the breath and devastating impact of muscle wasting due to its indirect association with other primary causes of disease. For example, it occurs in almost 80% of patients with advanced stages of cancer where it impairs mobility and causes up to 50% of cancer mortalities. Turmor burden as well as many anti-cancer treatments contribute to this wasting (a.k.a. cachexia), indicating that treating the tumor alone is an inherently insufficient approach. More than half of people over 80 suffer from sarcopenia, which increases the risk for hospitalization, disability and mortality. Heart failure prevalence exceeds 5.8 million in the US, 23 million globally, and like cancer, causes both muscle and the heart to waste away with fatal consequences. Injuries to muscle, tendons, ligaments, peripheral nerves and bones all cause muscle wasting and are the primary impediment to rehabilitation among military personnel. In fact, 24% of evacuations from the Iraq and Afghanistan wars resulted from non-combat musculoskeletal injuries whereas only 14% resulted from combat injuries. Possibly most devastating are the muscular dystrophies; degenerative and usually fatal diseases that are often first diagnosed in children.
Financial costs. The market potential for treating muscle wasting is enormous. Current costs for treating all muscle wasting diseases is ~ $550 billion, $93 billion for just cancer, yet there are currently no therapies for actually restoring muscle mass or strength. Many treatments increase appetite, but fail to significantly deter muscle wasting while some, corticosteroids, can even hasten muscle degeneration. Thus, novel therapeutics like AVGN7 could revolutionize the clinical treatment of many different disease states that ultimately produce muscle wasting.