A study using a mouse model suggests that some symptoms of Huntington’s disease are caused by muscle abnormalities, and are not related to dying neurons. The findings may present new opportunities for improving patient care by using muscle-specific drugs.
The study, “Progressive Cl− channel defects reveal disrupted skeletal muscle maturation in R6/2 Huntington’s mice,” was published in the Journal of General Physiology.
In earlier research, research teams at California State Polytechnic University and Wright State University in Ohio discovered that mice with an early Huntington’s disease onset have abnormal chloride ion movements in their muscles at late disease stages. This was caused by the lack of a protein called ClC-1. The team noted that the mRNA (the intermediate between gene and protein) was not processed correctly. This caused muscles to react even without the presence of the correct nerve signals.
While the early data suggested that muscle abnormalities could explain some symptoms of Huntington’s, such as involuntary movements, there was no way for the researchers to know if the muscle changes were caused by the death of neurons.
So in the new study, the team explored the muscles of Huntington’s mice from an early age, and followed the development as the disease progressed.
Comparing Huntington’s with healthy mice, they noted the ClC-1 protein was low in both mice groups at an early age. Also, in healthy mice the mRNA of the protein was not processed correctly, but as the mice grew older, healthy mice started producing the protein.
This suggested that the processing, which prevented the protein to be formed, was part of a normal course of development. It also indicated that the Huntington’s mice muscles did not mature the same as that of normal mice.
The team also found abnormalities in other muscle factors, including potassium. The potassium movements in the muscles were lower than in normal mice throughout the disease course.
The idea that Huntington’s muscles did not mature in a normal way, also was confirmed as the team found higher levels of a myosin muscle protein in older mice. This type of myosin is normally present only in newborns.
Exploring the changes, also in a mouse model with a later disease onset, the team found similar changes in ClC-1 and the newborn myosin. This indicates that muscle changes may explain some muscle symptoms also in adult onset Huntington’s disease.
“Our results support the idea that HD is a myopathy as well as a neurodegenerative disease and may provide a new opportunity to improve patient care by targeting skeletal muscle tissue,” Andrew Voss, senior author of the study, said in a press release.