A Smad7 Gene Therapy to Inhibit Age-Related Muscle Loss is in Development
There are always many ways to influence any specific process in cells and tissues. When it comes to enhanced muscle growth, the most popular approaches so far are myostatin inhibition, such as via gene knockout or the use of antibodies, or increased levels of the myostatin inhibitor follistatin. Both of these have been shown to greatly increase muscle mass in a number of species, and are thus potential treatments to compensate for the loss of muscle mass and strength that occurs over the course of aging. Physical weakness is a large component of age-related frailty, and even partially removing that part of the aging process is a worthy goal. The research group noted here has taken a different approach to this area of biochemistry, targeting smad7 to inhibit processes that break down muscle tissue:
"Chronic disease affects more than half of the world's population. It occurs with chronic infection, muscular dystrophy, malnutrition and old age. About half the people who die from cancer are actually dying from muscle wasting. What kills a lot of people isn't the loss of skeletal muscle but heart muscle. The heart literally shrinks, causing heart failure." In cachexia, tumors secrete hormones that cause muscle deterioration; in effect, the body eats its own muscles, causing weakness, frailty and fatigue. Researchers have long sought to stop this process, but failed to find a safe way. That's because the hormones that cause wasting - in particular, a naturally occurring hormone called myostatin - play important roles elsewhere in the body.
So researchers needed a way to stop myostatin, but only in muscles. Their solution: an adeno-associated virus - a benign virus that specifically targets heart and skeletal muscle. The virus delivers a small piece of DNA - a signaling protein called Smad7 - into muscle cells. Smad7 then blocks two signaling proteins called Smad2 and Smad3, which are activated by myostatin and other muscle-wasting hormones. By blocking those signals, Smad7 stops the breakdown of muscles. "Smad7 is the body's natural break and, by inhibiting the inhibitor, you build muscle." In 2015, the researchers launched AAVogen, a company that will develop this discovery into a commercial drug, AVGN7.
Link: https://news.wsu.edu/2016/07/26/scientist-develops-gene-therapy-muscle-wasting/