New technique targets gene that causes neurodegenerative disease

Neuroscientists at the University of Chicago studying a unique gene that expresses two proteins, one that is necessary for life and another, that when mutated causes a neurodegenerative disease called spinocerebellar ataxia type 6 (SCA6), have developed a technique to selectively block the disease-causing protein without affecting the other.

In a new study, published July 13, 2016, in Science Translational Medicine, the researchers show how they were able to use a modified virus to deliver a small sequence of RNA called micro RNA (miRNA) that blocked the expression of the mutated protein and prevented SCA6 from developing in mice. The technique could potentially be used to treat other diseases caused by mutations in so-called "bicistronic" genes that produce multiple proteins, including several forms of cancer.

"We were able to very surgically strike at the toxic portion of the gene and blunt the sharp end of the spear," said Christopher Gomez, MD, PhD, the Albina Y. Surbis Professor of Neurology at the University of Chicago and senior author of the study. "It's a technique for shutting down disease-causing genes that could have fewer off target effects."

SCA6 is an inherited neurodegenerative disease that strikes in middle age and causes patients to slowly lose coordination of their muscles and eventually their ability to speak and stand. Human genetic studies identified its cause as a mutation in CACNA1A-a gene that encodes a calcium channel protein important for nerve cell function. In 2013,