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An appetite for innovation: The hormone hypothesis for treating symptoms of anorexia and cachexia

By Dr Doug Witherspoon - 28th May 2023


The Dorsal View has reported previously on the surge in innovation when it comes to developing capsules that interact with our gut, such as the drug-free capsule that has been shown to treat chronic constipation.

Another such initiative has popped-up recently in the form of a capsule that can stimulate hunger-regulating hormones to help people suffering with anorexia, cachexia, and other chronic disorders that destroy the natural appetite for food. It’s another example of how collaborations between medicine and engineering have the potential to change the way we treat a range of conditions in the years ahead.

A team at MIT in the US has developed a capsule that can stimulate endocrine cells to produce ghrelin, a key appetite-stimulator. Hormones such as ghrelin, play an important role in appetite stimulation and are produced by endocrine cells that are part of the enteric nervous system, which is responsible for feelings of satiety, hunger, and nausea. This new approach delivers an electrical current to the cells, and it is hoped it can provide some appetite-enhancing effects in not only anorexia patients, but also those who have lost weight due to weight-wasting conditions, including cancer.

The researchers have dubbed the term ‘electroceuticals’ to describe the process. Basically, they began by using electrical probes on animal models and discovered that after 20 minutes of stimulation, ghrelin levels in the animals were markedly increased, and without any negative physiological effects.

Taking it a step further, they wondered if they could produce the same effects by using an ‘electroceutical’ pill that could be swallowed, temporarily reside in the stomach, and produce the same results. This approach comes with its own challenges, such as making sure the electrodes on the capsule can get in contact with the stomach tissue, which of course is coated with fluid.

Their simple, but ingenious, solution was to design the capsule with grooves on the surface that draw fluid away from the electrodes. As is often the case, nature provided the ‘light-bulb moment’ – the design was inspired by the Australian ‘thorny devil’ lizard, which has evolved with ridged scales on its skin that collect water. When the thorny devil touches water with any part of its skin, the fluid is automatically transported by capillary action along the channels and right to the lizard’s mouth.

As MIT graduate student and one of the lead authors, James McRae explained in the paper, which was published recently in Science Robotics, the surface of the capsule incorporates grooves with a hydrophilic coating, which serve as channels that draw fluid away from the stomach tissue. The capsule produces a battery-powered charge that results in an electric current that flows across electrodes on the surface of the capsule. In its current iteration, the charge runs constantly. However, it is hoped to produce future versions where the current can be wirelessly turned on and off.

McRae explains: “We were inspired by that [thorny devil] to incorporate surface textures and patterns onto the outside of this capsule. That surface can manage the fluid that could potentially prevent the electrodes from touching the tissue in the stomach, so it can reliably deliver electrical stimulation.”

Senior author of the study, Prof Giovanni Traverso, Associate Professor of Mechanical Engineering at MIT and Gastroenterologist at Brigham and Women’s Hospital, also commented: “This study helps establish electrical stimulation by ingestible electroceuticals as a mode of triggering hormone release via the GI tract. We show one example of how we’re able to engage with the stomach mucosa and release hormones, and we anticipate that this could be used in other sites in the GI tract that we haven’t explored here.”

If successfully developed, this little capsule could provide a much needed boost to the quality-of-life for people who are appetite-impaired and may already be on multiple medications.

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