Timothy J. Hines, PhD, Postdoctoral Associate at The Jackson Laboratory in Bar Harbor, Maine, shared an update on his CMTA and Uplifting Athletes funded research on CMT2D at the recent CMTA STAR Advisory Board meeting in Florida, USA.
CMT2D is caused by mutations in an enzyme called glycyl tRNA synthetase (GARS). In normal cells, GARS is involved in protein creation by providing one of the building blocks, called glycine. When GARS is mutated in CMT2D, it does not take the glycine building blocks where they need to go. This causes the protein creation process to stall and sets off a series of events in the cell known as the Integrated Stress Response. If we can stop this stress response from happening, we may be able to reduce some of the negative symptoms of CMT2D.
Working in mouse models of CMT2D, Tim was able to turn down one of the stress response activators called GCN2. This improved grip strength, body weight, and nerve conduction speeds in the mice, reducing some of their CMT symptoms.
The stress response causes the cell to stop making most proteins, but it also increases production of stress response genes. Scientists don’t know what the effects of these stress response genes are. To figure this out, Tim made CMT2D mice that have the stress response genes turned off. These mice showed improvements in the function of their nerves.
Katherine Forsey, PhD, the CMTA’s Chief Research Officer said “Tim’s work has revealed parts of the cell system that malfunction in CMT2D. The more we understand about these malfunctions, the more targets we have for potential treatments. The CMTA has committed funds to support The Jackson Laboratory as they continue their work across multiple CMT types. Together we are accelerating research, advancing our knowledge and identifying new targets for CMT treatments”.
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