Implantable Mini LEDs Stimulate Colonic Transit

December 22, 2017 - Gastroenterology & Endoscopy News

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If findings from a mouse study can be replicated in human trials, light-emitting diodes may prove to be an effective method for increasing gastrointestinal transit and treating motility disorders. Researchers in the United States and Australia have shown that LEDs that emit blue light can stimulate colonic contractions and propel feces through the GI tract.

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“This is fascinating stuff,” said William Chey, MD, professor of medicine, director of the GI Physiology Laboratory and co-director of the Michigan Bowel Control Program, at the University of Michigan Health System, in Ann Arbor. “If these results can be validated by other groups and in human subjects, the implications would be profound, since it could open the door to using this approach as a means of treating a variety of gastrointestinal motility disorders, including slow-transit constipation, gastroparesis and intestinal pseudo-obstruction.”

 

Senior investigator Nick Spencer, PhD, president of the Australasian Neurogastroenterology and Motility Society and professor in human physiology at the Flinders University School of Medicine, in South Australia, said optogenetics—the use of light to control living cells—is being explored for stimulation of the central nervous system, among other indications, but has not been applied to the GI tract. That’s surprising, Dr. Spencer added, given that the digestive tract possesses an independent nervous system. “It could be because delivering light to internal organs in conscious animals has proven to be challenging.”

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Dr. Spencer and his colleagues at Washington University in St. Louis, and Australia used light generated by wirelessly controlled and implanted miniature LEDs to activate specific populations of neurons in the enteric nervous system. The team, including Hongzhen Hu, PhD, of Washington University in St. Louis, genetically engineered mice to express a light-sensitive protein that is found in algae and develops only in excitatory neurons of the enteric nervous system.

 

“We did this so that pulses of blue light would activate only this population of excitatory neurons, which we found caused contraction of colon muscle that propelled ingested content through the intestine,” Dr. Spencer said (Figure). “The next part of our research will be to demonstrate that the same increases in colonic transit can be seen in nontransgenic animals.”

 

That seems possible given that adeno-associated viruses are being used in various gene therapies and can be injected into the intestinal wall to generate the same protein that the investigators produced through genetic engineering.

 

“This is very exciting because it means we would not need to genetically modify animals, including humans,” said Dr. Spencer, who presented the findings at the European Society of Neurogastroenterology and Motility’s NeuroGASTRO 2017 meeting (abstract 25).

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Dr. Spencer and Dr. Chey, who was not involved in the latest study, were enthusiastic about the possibility of a treatment for chronic constipation that could reduce the likelihood of adverse events that occur with existing drugs.

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“Stimulating the luminal compartment of the gastrointestinal tract directly could avoid the systemic side effects seen with orally administered, systemically absorbed prokinetic drugs, such as 5-HT agonists,” Dr. Chey said. “However, the findings need to be reproduced, and additional questions need to be answered, before we can consider optogenetics for clinical use.”

 

For example, further research should establish the appropriate frequency and duration of light treatment; whether optogenetics can be applied to other parts of the GI tract; and whether it can slow transit in the same way it accelerates transit, Dr. Chey said.

 

Dr. Spencer said the limitations of the technology in its current form are that the LEDs need to be surgically implanted and would only be useful for treatment of intractable long-term constipation, since it takes three to four weeks for the treatment to be effective.

He added that his team is exploring the use of optogenetics to “silence pain from the viscera, especially in patients with irritable bowel syndrome or long-term visceral pain of unknown origin.”  

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