image: Integrated circuit at the core of the BIOSYNC implant will interface to the cell reservoirs electrically and optically.
Credit: Yatin Gilhotra, Columbia Engineering
A multidisciplinary team led by Ken Shepard, a pioneering researcher in bioelectronics at Columbia Engineering, has won an award of up to $41 million from the Advanced Research Projects Agency for Health (ARPA-H) to build a wireless bioelectronic device to treat obesity and diabetes. The team was selected by ARPA-H’s Resilient Extended Automatic Cell Therapies (REACT) program to create bioelectronic devices that enable people to administer treatments of biologic drugs without the need for injections. Instead, engineered cells act as cell factories to produce the drugs, negating the need for the chemical modifications required to make such biologics shelf-stable, which often results in reduced efficacy.
As the first clinical application of this technology, the team is focusing on the biologics targeting type-2 diabetes (T2D) and obesity, working with Dr. Judith Korner and Dr. Rudolph Leibel in the Naomi Berrie Diabetes Center and Metabolic and Weight Control Center at Columbia University Irving Medical Center (CUIMC), which are at the forefront of research and treatments for T2D and obesity. T
Obesity a major issue in the U.S.
More than 70% of adults in the U.S. are either obese or overweight, and this has created an enormous health and economic burden. The persistent rise in obesity and T2D is shortening lifespans, increasing ongoing health issues, and inflating system-wide health care costs.
Meanwhile, effective non-invasive treatments are limited. Behavioral interventions have failed to produce sustained weight loss in the overwhelming majority of individuals with obesity, underscoring the importance of identifying not only new pharmacotherapies that promote sustained reductions in food intake and body weight, but also systems that can deliver these therapeutics with enhanced patient compliance and reduced incidence of adverse events.
BIOSYNC, a new way to treat obesity
With the ARPA-H funding, Shepard’s team plans to build an implantable device, named Bioelectronics for the Delivery of Synthetic Therapeutic with Wireless Control (BIOSYNC), that will reduce adverse events via temporal- and dose-controlled release of peptide satiety signals manufactured by implanted cells. The team, which includes leading researchers from Brigham and Women’s Hospital, Harvard University, MIT, Stanford University, University of Pennsylvania, and Immusoft, will use BIOSYNC to produce two peptide therapeutics simultaneously to regulate appetite through physiological satiety pathways.
Highly popular treatments for obesity and diabetes are the use of injected glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist therapeutics, such as semaglutide and tirzepatide. A major challenge for these treatments has been nonadherence, because of the need to inject the drug, and side effects such as nausea and vomiting. By using a combination of two alternative peptide therapeutics with shorter half-lives delivered intermittently by BIOSYNC, better satiety control should be achievable with reduced side effects and better adherence to therapy.
“The ultimate goal of BIOSYNC is to change the way biologic drugs are produced and delivered with the potential for impact on a large number of medical conditions which have been difficult to manage with small-molecule drugs,” says Shepard, Lau Family Professor of Electrical Engineering, Professor of Biomedical Engineering, and Professor of Neurological Sciences (in Neurosurgery) at Columbia University.
This growing list of conditions includes autoimmune and inflammatory diseases, allergies, cancer, and neurological, hematological, and respiratory disorders. Shepard has a long history of leveraging leading-edge electronics in the form of complementary metal-oxide-semiconductor (CMOS) integrated circuit bioelectronic devices. Most of his recent efforts have been directed to volumetrically efficient implants for brain-computer interfaces and wearable imaging systems; many of these same ideas are applied to BIOSYNC.
Multi-university collaboration
Collaborators at Stanford, Harvard, MIT, and Immusoft bring key capabilities in synthetic biology to engineer the cell lines contained in the device, while collaborators at Brigham and Women’s Hospital and University of Pennsylvania help to drive new techniques to sustain and isolate the cells in the device and perform the key animal studies required for regulatory approval. A goal of the project is to perform the first-in-human study at the Columbia University Irving Medical Center under the guidance of Drs. Korner and Leibel.
How BIOSYNC works
The proposed device is flexible and thin -- 1.12 cm × 1.84 cm × 1.8 mm -- and is designed to be implanted subdermally in a simple outpatient procedure in the upper arm. The closed-loop system will include cell lines, both islet β-cells and immune B cells, engineered by the researchers that bring unique physiologic properties to the problem. These cell types have complementary secretory capabilities and will be contained within two distinct cell reservoirs in the BIOSYNC implant.
BIOSYNC communicates wirelessly with a smart phone and is wirelessly charged. A key innovation is the use of a custom CMOS application-specific integrated circuit (ASIC) for all of the electronics of the BIOSYNC implant. This is essential to reduce the volume of the implant and provide the maximum volumetric efficiency, which the team defines as the ratio of the cell reservoir volume to the total implanted volume of the device -- for BIOSYNC, this is an unprecedented 38%.
“Our BIOSYNC system will have the ability to synthesize and maintain meaningful plasma concentrations of biologic compounds with operational control of drug dose, establishing a new approach for the delivery of biologic pharmaceuticals,” says Shepard.
ARPA-H
ARPA-H is a federal funding agency that accelerates better health outcomes for everyone by supporting the development of high-impact solutions to society's most challenging health problems. The Columbia Engineering team is one of four to receive the ARPA-H REACT funding.
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