Congenital myasthenic syndrome (CMS) is an overarching term for conditions that cause muscle weakness as a consequence of decreased communication between muscular and nervous systems.
For efficient communication, a signal (carried by a molecule known as acetylcholine) travels from the nervous system (specifically, cells called motor neurons) to skeletal muscle cells that are involved in movement. The signal causes the muscle cells to contract and the muscle to move. The skeletal muscle cells receive the signal through specialised structures known as acetylcholine receptors.
When the number of acetylcholine receptors is reduced, the signal cannot be efficiently relayed from motor neurons into the muscle, causing the condition called receptor deficiency-CMS. Receptor deficiency-CMS gets worse with physical exertion because, although the signal is being sent repeatedly from the nerve cell, it cannot trigger the muscles to move. Standardised treatments are available, but their efficiency is quite poor and rarely lead to an improved lifestyle for people living with CMS.
A protein called DOK7 is responsible for the positioning of acetylcholine receptors at the tips of skeletal muscle cells. Gene therapy that increases the amounts of DOK7 in mouse models has previously been shown to improve the physical activity of mice in models for the conditions DOK7-CMS, amyotrophic lateral sclerosis, spinal muscular atrophy, and age-related motor impairment.