Gen eraser: Will chronic diseases such as heart and kidney weakness soon be curable?

Gen eraser: Will chronic diseases such as heart and kidney weakness soon be curable?

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Cure chronic diseases with a new treatment approach

Chronic illnesses often accompany those affected for a lifetime and limit the quality of life and not seldom also life expectancy. Current treatments are largely aimed at alleviating and slowing the effects of the diseases. A main reason why many chronic diseases cannot be cured is that they have already caused changes in the genetic makeup. They keep the disease alive. A German team of researchers has now succeeded in simply erasing these epigenetic changes. They call their discovery a gene eraser.

Researchers in Göttingen have developed a new method that can be used to delete changes in the genome caused by chronic diseases. These changes are responsible for the course of the disease in many chronic conditions such as heart failure or kidney failure. The study results were recently published in the renowned journal "Nature Communications".

The cause is in the genes

Difficulty breathing up to shortness of breath, chronic fatigue, water retention in the limbs - these are, among other things, typical symptoms with which sufferers of heart or kidney weakness constantly have to struggle. With increasing age, the complaints become increasingly clear as the performance of the organs decreases. The basis for these diseases are so-called epigenetic changes. These are modifications that subsequently change the genetic material (DNA) and have partially made it unusable. This is due to chemical processes with which, for example, certain molecules have been coupled to DNA (DNA methylation).

Erase instead of cut

The team around Professor Dr. Michael Zeisberg of the University Medical Center Göttingen has succeeded for the first time in reversing these pathogenic changes. The researchers further developed the technology known as “gene scissors”. "Instead of cutting the DNA, the modified technology can now be used to clean a gene segment from the modification like with an eraser," Zeisberg explains in a press release on the study results.

Simply erase chronic diseases

As the researchers report, this new method can be used to correct both DNA methylation and fibroblasts that are responsible for the course of the disease. Fibroblasts are fibrous or connective tissue formation cells that are responsible for the regeneration and remodeling of connective tissues. If there is an epigenetic change, the fibroblasts also expel epigenetically modified DNA, which can then even be detected in the blood. "Potential epigenetic modifications in the kidney or in the heart can be identified with a simple blood test and then corrected with a tailored therapy," write the genetic experts.

Personalized treatment for heart or kidney weakness

This method represents a new approach to personalized therapy for heart failure and chronic kidney failure. "The results of this study give hope that we will have another effective method for treating heart failure in the future," adds Professor Dr. Gerd Hasenfuß, the chairman of the heart center. With this method, a wide range of applications is possible to regulate the activity of individual genes. The big advantage: You don't have to change the actual sequence of inheritance, you just have to undo harmful changes.

The DNA reset

The principle of gene scissors was discovered in bacteria that rid themselves of harmful viruses by directing a certain protein (Cas9) to an arbitrary position in the DNA and severing the double strand at this point. "For our purposes, we have modified the Cas9 enzyme in such a way that it can still bind specific gene segments but no longer has the ability to cut them," explains Zeisberg. The researchers coupled the CAS9 protein with another enzyme called Tet3. The effect: instead of cutting the DNA, pathogenic modifications were removed and the original state of the DNA sequence was restored.

So far only tested in animal models

"The study demonstrated for the first time the successful application of this method in animal models," says the research team. The researchers are currently working on making the modified enzyme more compact. After that, it should also be tested on human patients. (vb)

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