Myostatin inhibition via ActRIIB-Fc increases muscle mass by 20–31% in neonatal control mice but results in minimal muscle mass gains (≤74%) and no functional improvement in severe SMA mice, demonstrating a blunted response to muscle growth stimulation in severe SMA.

In severe spinal muscular atrophy, muscles are already shrinking and struggling to grow, so they naturally increase signals that promote growth and reduce signals that block it. When a drug tries to block the growth-blocking signal even more, the muscles cannot respond because they are already working at their maximum capacity to grow. At the same time, the drug also causes fat loss, which makes the body even weaker and less able to survive, so any small muscle gain is canceled out by overall decline.