The body regulates its metabolism in a precise and continuous way, with specialized cells in the pancreas constantly monitoring the amount of blood sugar, for example. When this level of blood sugar increases after a meal, the body starts a signal waterfall to lower it.
In people suffering from diabetes, this regulatory mechanism no longer works exactly as it should. Therefore, those affected have too much blood sugar and need to measure their blood sugar level and inject with insulin to regulate it. This is a relatively inaccurate approach compared to the body’s own mechanism.
Equip cells with special functions
Martin Fussenegger is a professor of biotechnology and bioengineering in the Department of Science and Engineering of Eth Zurich Biosystems in Basel. With the previous situation in mind, he and his team have been working on cell therapies for some time. One day, the hope is that these therapies allow metabolic diseases, such as diabetes to be treated individually and precisely, or even cured.
But how do these cell therapies work? First, researchers modify human cells by incorporating a network of genes that give cells special skills. These cells are implanted under the skin, for example, and the network is activated by a specific external stimulus.
An adequate switch is the key
To that end, researchers have developed several types of switches in recent years. Some can be electrically controlled, others with light and one even using music from the British rock band Queen (see eth news).
Basel researchers have now developed another variant, who have presented in the magazine Biomedical Engineering of Nature.
“For me, this solution is the best genetic switch that my group and I have built so far,” says Fussenegger. The reason is that the switch can be activated using the nitroglycerin of long -standing active ingredients, and that the means of application, sticking a patch to the skin, is very simple. The corresponding patches are already available to buy in various sizes in any pharmacy.
Nitroglycerin is quickly spread outside the patch towards the skin, where it finds an implant that contains modified human renal cells.
Nitric oxide network
These cells specifically intercept nitroglycerin and have an incorporated enzyme that makes it nitric oxide (NO), a natural signaling molecule. In the body, none normally causes blood vessels to dilate, which leads to greater blood flow. It decomposes in a few seconds and, therefore, only affects a very localized area.
The implanted cells are modified so that it does not trigger the production and release of the LPG-1 chemical messenger, which in turn increases the release of insulin by the beta cells of the pancreas and, therefore, regulates the level of sugar in the blood. LPG-1 also triggers a feeling of satiety, thus reducing food intake.
The new switch is performed exclusively with human components, that is, it does not contain components of other species. “That is a new and innovative feature,” says Fussenegger. With components of other species, there is always a risk of false trigger, interference with the body processes themselves or immune reactions. “Here, we can discard that.”
An entire switch arsenal
In the last 20 years, Professor ETH has developed several different genetic switches, some of which respond to physical triggers such as current, sound waves or light. What kind does the best opportunity to be implemented one day?
“Physical triggers are interesting because we do not need to use molecules that interfere with the body’s own processes,” says the biotechnologist. He explains that electrical signals are ideal for controlling switches and gene networks that use portable electronics such as smartphones or smart watches, and AI can also be incorporated. “Therefore, I think that electrogenetic cell therapies have the best implementation possibilities. In terms of chemical switches, I see that the new solution is in the Pole position,” says Fussenegger.
However, the additional development of these cell therapies based on gene switches is a complex and long process. “Developing a cell therapy for market expiration not only has decades but also requires a lot of personnel and sufficient resources,” says the researcher. “There is no shortcut.”
Until now, Fussenegger’s work has focused mainly on cell therapies for diabetes, which is one of the most frequent metabolic diseases in the world, which affects one in ten people. “That is the model disease we work with. Fundamentally, however, it is also possible to develop cellular therapies for other metabolic, autoimmune or even neurodegenerative diseases, in principle, for everything that requires dynamic regulation.” According to Fussenegger, many drugs are like a hammer that is used to hit a blind problem. “Cell therapies, on the other hand, solve the problem similar to the body,” he says.
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