Scientists at the UCL Queen Square Institute of Neurology in London have identified a new potential therapeutic strategy for CMT type 2D (CMT2D) that may be more broadly effective for treating neuropathy.
CMT2D is caused by mutations in the GARS1 gene, which produces a protein called glycyl-tRNA synthetase that is required by all cells. It is currently a mystery why mutations in GARS1 cause CMT. To better understand CMT2D, the Sleigh and Schiavo Laboratories have used cutting-edge imaging techniques to study mouse models of the disease. Their work reveals that an essential and continually active process in nerve cells known as ‘axonal transport’ is disrupted in the CMT2D mice, contributing to the disease.
Nerve cells have a long, thin tunnel-like structure called an axon, which helps to deliver electrical signals over long distances. For nerves to function correctly and survive, they require many substances to be transported up and down the inside of axons. In particular, motor and sensory neurons rely on this process to deliver critical survival factors from muscles towards the spinal cord.
The London-based researchers identified that delivery of these survival factors is impaired in CMT2D mice and is linked to a reduction in the activation in motor neurons of an important protein for nerve cell survival.
Through experiments that identified the cause of this transport disruption, the scientists were able to develop a treatment strategy that improves this critical transportation system in CMT mice, restoring function back to healthy levels. This approach involves boosting the availability of a vital protein called BDNF in CMT2D muscles.
Further work is currently underway to determine whether correcting the disruption in axonal transport is able to improve symptoms of neuropathy in CMT2D mice and whether this approach could be useful in other subtypes of CMT.
Published: May 22, 2023