Innovative Ingestible Devices for Targeted Metabolic Disease Treatments

A collaborative team of researchers from MIT is spearheading an innovative initiative, backed by a grant of $65.67 million from the U.S. Advanced Research Projects Agency for Health (ARPA-H). The project aims to develop ingestible devices that could revolutionize the treatment of diabetes, obesity, and other conditions through the oral delivery of mRNA. This technology also holds promise for needle-free administration of mRNA vaccines.

Exploring Electroceuticals for Metabolic Disorders

Over a five-year period, the project will explore the development of electroceuticals—novel ingestible therapies that utilize electrical stimulation to engage the body’s natural hormonal and neural signaling pathways. If successful, this method could pave the way for innovative treatments targeting various metabolic disorders.

Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, emphasizes the advantages of oral administration, which is often preferred by both patients and healthcare providers. The primary focus will be on metabolic disorders due to their widespread impact, although the technology being developed could have far-reaching applications.

Leading Experts and Collaborative Efforts

Leading the research, Traverso collaborates with notable figures including Robert Langer, an MIT Institute Professor, and Anantha Chandrakasan, dean of the MIT School of Engineering. The team will also work alongside researchers from Brigham and Women’s Hospital, New York University, and the University of Colorado School of Medicine.

At MIT, Langer will contribute by developing nanoparticles for mRNA delivery while Chandrakasan focuses on minimizing energy consumption and miniaturizing electronic functionalities within the capsules, including secure communication and power generation.

Breakthroughs in mRNA Delivery Technologies

In recent years, Traverso and Langer’s labs have engineered a range of ingestible devices designed to effectively deliver medications to the gastrointestinal tract. This technology is particularly valuable for protein drugs and nucleic acids that typically cannot be administered orally due to degradation in the acidic digestive environment.

Messenger RNA has already demonstrated its utility as a vaccine, instructing cells to generate viral protein fragments that activate immune responses. The capacity to deliver mRNA to cells opens up possibilities for stimulating the production of therapeutic molecules for a variety of diseases, with a special emphasis on metabolic conditions like diabetes.

“What mRNA can do is enable the potential for dosing therapies that are very difficult to dose today, or provide longer-term coverage by essentially creating an internal factory that produces therapy for an extended period.” — Giovanni Traverso

As part of the mRNA segment of this project, the research team aims to identify optimal lipid and polymer nanoparticle formulations for effective mRNA delivery. They will leverage machine learning techniques to assist in identifying the most promising candidates. Additionally, they plan to design and test ingestible devices capable of transporting mRNA-nanoparticle complexes, with aspirations to conduct a clinical trial in the project’s final year.

This effort builds on existing research; in 2022, Traverso and colleagues successfully demonstrated mRNA delivery via capsules that inject mRNA-nanoparticle complexes into the stomach lining.

Electrical Stimulation Therapies

The project will also investigate ingestible devices that can administer small electrical currents to the stomach lining. In a groundbreaking study published last year, Traverso’s lab showcased this approach using capsules equipped with electrodes to deliver electrical stimulation to stomach cells. Their findings indicated that this stimulation increased the production of ghrelin, a hormone associated with appetite stimulation.

Traverso envisions that such treatments could either replace or complement existing medications used to manage nausea and stimulate appetite in individuals facing conditions like anorexia or cachexia—often seen in cancer patients or those with chronic diseases. Moreover, researchers aim to explore methods for enhancing the production of GLP-1, a hormone that plays a crucial role in diabetes management and weight loss.

“This approach maximizes our ability to treat diseases without introducing new drugs but by modulating the body’s own systems through electrical stimulation,” Traverso explains.

Multidisciplinary Collaboration and Ethical Insights

The Brigham and Women’s Hospital team will be co-led by Traverso alongside Ameya Kirtane, Jason Li, and Peter Chai. Their efforts will concentrate on mRNA nanoparticle formulation and stabilization, device engineering, and executing clinical trials. At NYU, assistant professor Khalil Ramadi will lead research into the biological effects of electrical stimulation. Researchers from the University of Colorado will investigate ethical considerations and public perceptions regarding these advanced biomedical interventions.

“We believe we have a unique opportunity not only to conduct fundamental engineering science and early-stage clinical trials but also to understand the ethical implications and public attitudes surrounding these technologies through this comprehensive collaboration,” says Traverso.

This groundbreaking project is supported by ARPA-H under award number D24AC00040-00. The information presented here may not reflect the official views of the Advanced Research Projects Agency for Health.