Simple skin patches can control next-generation cell therapy for diabetes

Hundreds of years of heart drugs may be the key to revolutionizing how we provide advanced cellular therapies. Scientists at Eth Zurich have developed a clever system that uses nitroglycerin plaques (the same ones targeting heart disease since the 1890s) to control genetically engineered cells that can produce therapeutic proteins based on demand.

This innovation, detailed in natural biomedical engineering, could transform millions of treatments for type 2 diabetes and other chronic diseases. The system precisely controls the production of therapeutic proteins by applying or removing plaques from the skin.

“For me, this solution is the best genetic switch that my group and I have built so far,” said Martin Fussenegger, professor of biotechnology and bioengineering in the Department of Biosystems Science and Engineering at Eth Zurich, Basel. The beauty of the method lies in its simplicity – the patient can easily apply the plaque itself, while the drug spreads rapidly through the skin to activate the implanted therapeutic cells.

In a trial in diabetic mice, the system maintained healthy blood sugar levels for 35 days by triggering the controlled release of GLP-1, a hormone that stimulates insulin production. The treated mice showed normalized insulin levels and weight reduction without the cardiovascular side effects associated with nitroglycerin.

The innovation builds on the growing field of cell therapy, where human cells are modified as factories of living matter in the body. While there is hope, these therapies face challenges in controlling when and how many drugs are produced. This new switch provides precise control through familiar medical devices – skin patches.

The system works through a range of natural human cell components. When the plaque’s nitroglycerin reaches the engineered cells implanted under the skin, they convert it to nitric oxide, a natural signaling molecule. This triggers cells to produce therapeutic proteins (such as GLP-1) for diabetes treatment.

It is worth noting that the entire system is constructed using only human proteins and cellular mechanisms, thus reducing the risk of immune responses that may occur with components of other species. Researchers have demonstrated that treatment effects can be reliably started and stopped by applying or removing plaques, allowing patients and doctors to precisely control treatment.

For one-tenth of people worldwide affected by diabetes, this method can be an alternative to regular injections. Instead of repeated use of artificial insulin or GLP-1 drugs, the patient’s body can naturally produce these proteins and regulated by simple plaques.

These implications go beyond diabetes. “Fundamentally, it is possible to develop cellular therapies for all other metabolism, autoimmune and even neurodegenerative diseases that require dynamic regulation,” Fussenegger explained.

However, the path to human treatment is still long. “Developing cell therapies to market maturity takes not only decades, but also a large number of employees and adequate resources,” Fussenegger notes. “There is no shortcut.”

Nevertheless, the system is a major advancement in making cell therapy more practical and patient-friendly. As Fussenegger said, many current drugs work like “a hammer used to solve problems blindly”, and “cell therapy solves the problem in a similar way to the body.”

The next step of the research team will focus on further testing and improvement of the system and work on the final clinical trial. If successful, the marriage between cardiology and genetic engineering in the 19th century may usher in a new era of cell therapy for chronic diseases.