Promising new research on Huntington's disease

Huntington's disease is a dreaded and debilitating congenital neurological disorder. There are little successful treatments and no cure. But a special type of brain cell forged from stem cells could help restore the muscle coordination deficits that cause the uncontrollable spasms characteristic of the disease.

"This is really something unexpected," Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist said.

Zhang and his colleagues at the UW-Madison Waisman Center have learned how to make large amounts of GABA neurons from human embryonic stem cells, which they sought to test in a mouse model of Huntington's disease. The goal of the study, Zhang notes, was simply to see if the cells would safely integrate into the mouse brain. To their astonishment, the cells not only integrated but also project to the right target and effectively reestablished the broken communication network, restoring motor ability. It showed that locomotion could be restored in mice with a Huntington's-like condition.

What researchers found was intriguing, because GABA neurons reside in one part of the brain, the basal ganglia, which plays a key role in voluntary motor coordination. But the GABA neurons exert their influence at a distance on cells in the midbrain through the circuit fueled by the GABA neuron chemical neurotransmitter.

"This circuitry is essential for motor coordination," Zhang said, "and it is what is broken in Huntington patients. The GABA neurons exert their influence at a distance through this circuit. Their cell targets are far away."

That the transplanted cells could effectively reestablish the circuit was completely unexpected: "Many in the field feel that successful cell transplants would be impossible because it would require rebuilding the circuitry. But what we've shown is that the GABA neurons can remake the circuitry and produce the right neurotransmitter."

The study suggests that it may one day be possible to use cell therapy to treat Huntington's, but also because it suggests the adult brain may be more malleable than previously believed.

Zhang stresses that while the new research is promising; working up from the mouse model to human patients will take much time and effort. But for a disease that now has no effective treatment, the work could become the next best hope for those with Huntington's.