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Gut re-action

Remaking the enteric nervous system

A group of New York academics has developed a protocol to turn human pluripotent stem cells into gut neurons, and believes it could provide the first non-surgical treatment for Hirschsprung's disease - a rare disorder in which the large intestine develops without the neurons that normally control peristalsis. But the system could have more far-reaching implications, most notably for using the cells to test CNS drug candidates for GI side effects.

The enteric nervous system controls the wave-like muscle contractions that move food through the digestive tract. It contains a few dozen cell types and, in total, has more neurons than the spinal cord. But in Hirschsprung's disease, the neural precursors that normally migrate into the lower GI tract and give rise to the enteric nervous system fail to do so.

The disease typically affects the most distal segment of the colon which fails to relax properly after contractions, preventing peristalsis, and becomes blocked. It is usually diagnosed a few days after birth when an infant fails to have its first bowel movement, and is most commonly treated by surgery to remove the dysfunctional part of the colon.

However, Lorenz Studer, who led the New York group and is director of the Center for Stem Cell Biology and member of the Developmental Biology Program at Memorial Sloan Kettering Cancer Center (MSKCC), told BioCentury that in rare cases neurons are lost from the entire length of the large intestine. Those patients cannot undergo surgery and must receive IV nutrition, he said. "Those kids don't have other options; with them, you might have a real chance to offer something."

Studer told BioCentury his

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