Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations

Nemaline myopathy (NM) is the most common non-dystrophic congenital myopathy and is most frequently caused by mutations in the nebulin gene. The sarcomeric protein nebulin plays a crucial role in skeletal muscle performance. NM patients with nebulin mutations have muscle weakness through mechanisms including a lower responsiveness to calcium. No therapy exists to treat muscle weakness in NM. Here, we show that the novel fast skeletal muscle troponin activator, CK-2066260, augments force generation at submaximal calcium levels – levels that are typically used for daily life activities. Thus, fast troponin activation is a therapeutic mechanism to augment muscle strength in NM patients with nebulin mutations. (By Dr. Josine de Winter, http://jmg.bmj.com/content/early/2013/04/08/jmedgenet-2012-101470 )