An excessive amount of mechanical sensation in the neurons that sense the limbs in space can lead to locomotor deformities such as arthrogryposis.
Their research also provides proof of concept that reducing this highly sensitive neuronal activity (via Botox or a special diet) at a critical age may be a viable way to non-invasively treat some musculoskeletal disorders.
What is distal arthrogryposis?
Distal arthrogryposis (DA) is a disorder characterized by congenital joint deformities or contractures, often limiting movement in the hands and feet, and affecting approximately one in 3,000 people worldwide. Invasive surgery is often required to relieve symptoms.
Although mutations in genes related to muscle and joint function have been linked to DA, patients have been found to have gain-of-function mutations in PIEZO2, a key mechanosensor in sensory neurons that underlie touch, proprioception, and other mechanosensory processes. with DA subtype 5 (DA5). However, the mechanism by which PIEZO2 mutations cause DA is unknown.
Using a mouse model, Shang Ma and colleagues found that overexpression of a mutant PIEZO2 gain-of-function allele in proprioceptive neurons that innervate muscles and tendons during a critical postnatal period during development can cause joint contracture. These defects did not occur when the dysfunctional allele was expressed in skeletal muscle, cartilage, or tendon.
“It is reassuring to find that expression of a gain-of-function allele of PIEZO2 in young adult mice does not cause DA symptoms. This narrows the window for potential therapeutic intervention that could lead to lifelong improvement for affected patients,” said Ma. and b.