New Pill Regulates Appetite by Modulating Ghrelin Release

Summary: A new pill, called FLASH, has been developed to regulate appetite without drugs or invasive procedures.

Researchers designed the pill to deliver electrical impulses to the stomach lining, modulating hunger-related gut hormones. The pill has been shown to affect the release of appetite hormone ghrelin in pig trials. FLASH could potentially treat various disorders related to metabolism and eating without pharmaceuticals or surgery.

The researchers are now conducting additional preclinical testing and aim to start human trials within five years.

Source: NYU

A new electrical “pill” may be able to regulate people’s appetites without any drugs or invasive medical procedures, a promising advancement in treating eating disorders and other medical conditions that benefit from adjusting someone’s food intake.

Developed by a research team from NYU Tandon School of Engineering and the Massachusetts Institute of Technology (MIT), the pill, dubbed FLASH, delivers electrical impulses to the stomach lining once it’s swallowed. This targeted stimulation triggers the brain to modulate gut hormones related to hunger. 

In a study published in Science Robotics, the researchers revealed they were able to affect the release of the ghrelin – an appetite hormone – using FLASH in pig trials, by orally administering a single pill. 

“The gut and brain communicate through a neural pathway known as the gut-brain axis, which regulates many bodily functions, including eating,” said Khalil Ramadi, Assistant Professor of Bioengineering at NYU Tandon and the Director of the Laboratory for Advanced Neuroengineering and Translational Medicine at NYU Abu Dhabi. Ramadi is the co-first and co-corresponding author on the study. 

“FLASH is the first ingestible electronic device shown to engage with the gut to modulate hormones that regulate brain activity on the gut-brain axis. By using the nervous system  to alter the release of certain gut hormones, FLASH can potentially treat a host of disorders related to metabolism and eating without pharmaceuticals or surgery. This is a big step forward in how we approach these diseases,” Ramadi said.

People with some medical conditions use appetite stimulants and anti-nausea medications to help increase their food consumption, said Ramadi, but that can produce unwanted side effects such as restlessness, fatigue, uncontrolled weight gain, headaches, and muscle spasms.

While electrical stimulation of the gastrointestinal tract can increase appetite, this approach has typically required surgery, which comes with inherent risks. The effectiveness of this method may be limited by the presence of fluids in the stomach and intestines, too. 

Alternative approaches, such as deep brain stimulation and vagus nerve stimulation, have shown success in regulating appetite but also involve invasive surgical procedures.

FLASH, with the absence of any side effects and no surgical intervention needed, overcomes drawbacks of those conventional methods used to boost appetite. Its design is also noteworthy, featuring a unique surface that mimics the water-wicking skin of a thorny devil lizard. This innovative feature shields the capsule from degradation and enables it to operate effectively within the highly wet environment of the gastrointestinal tract.

“FLASH represents a breakthrough for several reasons,” said Giovanni Traverso, Associate Professor in the Department of Mechanical Engineering at MIT, who collaborated with Ramadi on the research.

 “First, it proves that pills don’t have to contain drugs, and can instead be designed to deliver electrical impulses to regulate physiology. Unlike drugs which have broad uptake in the gut, electrical pulses can be designed to target specific cells and locations for targeted therapy.

“A second crucial innovation is the surface design. The gut lining is an extremely wet environment, which presents difficulty when trying to deliver electricity. Looking to nature, we find other scenarios where micro-patterned surfaces can wick fluid, enabling sturdy electrical connections in the body” said Traverso.

According to Ramadi, initial research demonstrates FLASH’s efficacy in increasing hunger, making it potentially therapeutic for eating disorders such as anorexia and Avoidant Restrictive Food Intake Disorder (ARFID). 

This shows a person eating salad
According to Ramadi, initial research demonstrates FLASH’s efficacy in increasing hunger, making it potentially therapeutic for eating disorders such as anorexia and Avoidant Restrictive Food Intake Disorder (ARFID). Credit: Neuroscience News

But, by adjusting the type and location of stimulation, the technology may be able to modulate hormones in the opposite direction, reducing overall hunger and providing a treatment for metabolic disorders like obesity or diabetes. With further development it could potentially treat neuropsychiatric disorders, like depression or substance addiction, too.

FLASH’s research team is currently conducting additional preclinical testing with the goal of beginning human trials with an advanced prototype within 5 years. 

This study adds to Ramadi’s path breaking body of work that advances the field of electrical ingestibles to treat diseases. Earlier this year, he and a group of colleagues announced successful trials of an electromagnetic “pill” that provides a window into the gastrointestinal tract using MRI machine-like technology. In 2021, he presented his work on electronic ingestibles as a TED Fellow. 

Ramadi is the co-first and co-corresponding author on the paper published in Science Robotics. Along with Traverso, his other MIT collaborators on the research are: James C. McRae, George Selsing, Arnold Su, Rafael Fernandes, Maela Hickling, Brandon Rios, Sahab Babaee, , Seokkee Min,  Declan Gwynne, Neil Xi-Juna Jia,  Aleyah Aragon, Keiko Ishida, Johannes Kuosmanen, Josh Jenkins, Alison Hayward and Ken Kamrin. 

About this neuroscience research news

Author: Leah Schmerl
Source: NYU
Contact: Leah Schmerl – NYU
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation” by Khalil Ramadi et al. Science Robotics


Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation

The gut-brain axis, which is mediated via enteric and central neurohormonal signaling, is known to regulate a broad set of physiological functions from feeding to emotional behavior.

Various pharmaceuticals and surgical interventions, such as motility agents and bariatric surgery, are used to modulate this axis. Such approaches, however, are associated with off-target effects or post-procedure recovery time and expose patients to substantial risks.

Electrical stimulation has also been used to attempt to modulate the gut-brain axis with greater spatial and temporal resolution. Electrical stimulation of the gastrointestinal (GI) tract, however, has generally required invasive intervention for electrode placement on serosal tissue.

Stimulating mucosal tissue remains challenging because of the presence of gastric and intestinal fluid, which can influence the effectiveness of local luminal stimulation.

Here, we report the development of a bioinspired ingestible fluid-wicking capsule for active stimulation and hormone modulation (FLASH) capable of rapidly wicking fluid and locally stimulating mucosal tissue, resulting in systemic modulation of an orexigenic GI hormone.

Drawing inspiration from Moloch horridus, the “thorny devil” lizard with water-wicking skin, we developed a capsule surface capable of displacing fluid.

We characterized the stimulation parameters for modulation of various GI hormones in a porcine model and applied these parameters to an ingestible capsule system. FLASH can be orally administered to modulate GI hormones and is safely excreted with no adverse effects in porcine models.

We anticipate that this device could be used to treat metabolic, GI, and neuropsychiatric disorders noninvasively with minimal off-target effects.

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