Charcot-Marie-Tooth Disease, Type 1A

Charcot-Marie-Tooth Disease (CMT) is a neurogenetic disease, which affects 20-30 out of 100.000 people. Typical symptoms of the disease are difficulties in walking, foot deformities, sensitivity disturbances like numbness, tingling or pain, muscle spasms, loss of strength in the extremities and muscle wasting.

Difficulties in walking and foot deformities can occur as early as in childhood. Paralyses that develop during the course of the disease lead to functional impairment of the patients and in rare cases patients become bound to wheelchairs.

CMT does not result from a failure of the muscles as such but is caused by a non-sufficient transmission of nerve impulses from the brain to muscles. Due to mutations in the genes that affect the nerves, the axon of the nerve cells or the myelin layer which surrounds the axon is damaged resulting in the disturbance of neuronal impulses.

There might be several genetic causes for the disease. In the most common form, CMT 1A (70% of all CMT cases), the primary reason is a hereditary duplication of the gene coding for the protein PMP (Peripheral Myelin Protein) on chromosome 17. The increased production of PMP leads to thickening of the myelin sheath surrounding the axons of the nerve cells. Thus, in the long run, the myelin sheath and/or the axon is damaged, most probably by the impediment of nutrient supply. This leads to obstruction of transmission of the impulses in peripheral nerves and brain signals cannot reach the muscles any longer. The consequence of this “denervation” is muscles weakness and reduction of muscle mass. The more the myelin layer is damaged, the lower is the transmission speed of the nerves and the more severe are the disease symptoms.

For treatment of CMT 1A it is very important that the production of PMP is not suppressed completely but downregulated to a healthy level.

This can be achieved by a mechanism of action of UgimersTM called “steric block” that can downregulate protein translation by about 60%. UgimersTM that downregulate PMP production to the level of healthy people are in development.