Lower motor neurons of the spinal cord are the main cell type affected by SMA. When the lower motor neurons deteriorate, they no longer efficiently contact their target muscles, ultimately leading to loss of voluntary muscle contraction, which causes muscle wasting, or atrophy, due to inactivity.
The goal of muscle protection is to protect the muscles from atrophy, increase muscle mass, and perhaps even restore some muscle function. Similar to neuroprotection, this strategy does not address the underlying genetics of SMA, rather, the aim is to slow or stop the progression of the disease. It could be used in combination with approaches designed to increase SMN protein levels.
It is thought that these approaches may be more appropriate for milder types of SMA. They may include:
Reldesemtiv is being studied in clinical trials for people with SMA by Cytokinetics. The results of their phase 2 clinical trials showed dose- and concentration-dependent increases in time to muscle fatigue as measured by changes from baseline in Six Minute Walk Distance (6MWD), a sub-maximal exercise test of aerobic capacity and endurance and Maximal Expiratory Pressure (MEP), a measure of strength of respiratory muscles, after eight weeks of treatment with reldesemtiv.
This study provides the first data indicating that a muscle-directed therapy, namely a fast skeletal muscle troponin activator, may be clinically beneficial in patients with SMA. This data is especially encouraging given the unmet need among those adolescent and adult individuals with SMA who have persistent muscle weakness, fatigue and functional impairment.