New therapeutic approach against previously incurable lung fibrosis

New therapeutic approach against previously incurable lung fibrosis

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The body's own protein reverses scarring in the lungs

Pulmonary fibrosis is a chronic disease that causes scarring of the lungs. So far, the disease has not been curable. But German researchers are now reporting on a possible approach to treating the dangerous lung disease.

Incurable lung disease

"The term pulmonary fibrosis (" scar lung ") summarizes a variety of different clinical pictures," explains the lung information service at the Helmholtz Zentrum München on its website. So far, the chronic lung disease, which is more deadly than many forms of cancer, has not been curable. But German researchers are now reporting on a possible approach to treating the dangerous disease.

Body's protein

The body's protein RAGE, which has so far mostly been noticed negatively in connection with chronic inflammation and diabetic consequential damage, plays a major role in the repair of damage in the genetic material (DNA).

It can obviously also cause tissue damage to heal as a result of accelerated cell aging.

Scientists at Heidelberg University Hospital and the German Center for Diabetes Research have now discovered this. They describe the molecular mechanism in the current issue of the journal "Nucleic Acids Research".

Fibrosis has so far been considered irreversible

They came across the possible therapeutic benefits of the protein in mice that cannot form RAGE: as a result of the limited genetic repair, these develop pronounced scarring in the lungs, known as pulmonary fibrosis.

After treatment with the protein, the scarring healed.

“This is astonishing in that fibrosis has so far been considered irreversible. With RAGE we could for the first time have found a possible starting point for healing this frequent tissue damage, ”said senior author Professor Dr. Peter Nawroth, Medical Director of the University Clinic for Endocrinology, Metabolism and Clinical Chemistry Heidelberg, in a message.

"Many questions - e.g. how this healing works in detail - are still open. "

Flawless repair of serious DNA damage

RAGE (Receptor of Advanced Glycation Endproducts) is well known in medical research.

The protein plays a crucial role not only in diabetes but also in chronic and excessive inflammatory reactions such as atherosclerosis and blood poisoning (sepsis), but also in Alzheimer's dementia and cancer.

The protein is mainly active on the surfaces of tissue and immune system cells.

On the other hand, inside the cells, more precisely in the cell nucleus, RAGE shows a completely different side of itself: Here it is responsible for the error-free repair of serious DNA damage, the so-called double-strand breaks, as the Heidelberg research team found.

In the case of this damage, the two linked and twisted strands of genetic information are completely cut off, and the cell would quickly perish without prompt repairs.

Scarred tissue regenerated

Since the DNA in the cells is read continuously - it contains the master plan for all processes in the cell - and is claimed, damage is extremely common: in every cell of the body there are probably arithmetic defects in this vital molecule several thousand times a day.

Disruptions in the complex repair mechanisms, for example because the cells are particularly exposed to environmental toxins or harmful metabolic products, can lead to the rapid aging, degeneration and scarring of entire tissue groups.

Examples are liver fibrosis in the case of alcohol abuse or retinal and kidney damage in the sugar disease diabetes mellitus.

There are currently no usable active ingredients to specifically correct malfunctions of these repair mechanisms and to damage tissue e.g. to prevent diabetes.

Mice that cannot develop RAGE due to a genetic defect develop, among other things, lung fibrosis.

The lungs are particularly susceptible to tissue damage because they are in constant contact with the outside world through the air they breathe and are particularly exposed to environmental influences.

In the animal model, the researchers succeeded in elucidating the as yet unknown molecular mechanism of DNA repair with RAGE involvement and in identifying important other protagonists.

With the help of modified viruses, they infiltrated RAGE into the lungs of the mice, not only did DNA repair normalize: to the surprise of the scientists, the scarred tissue regenerated and regained part of its functionality.

Molecular therapy to repair genetic and cell damage

The published work not only provides important insights into the molecular relationship between RAGE-mediated DNA repair, cell aging and fibrosis.

"For the first time, molecular therapy to repair genetic and cell damage in the lungs and thus prevent fibrosis or tumors, which also occur as a result of DNA damage, may be within reach," explains lead author Dr. med. Varum Kumar, University Clinic for Endocrinology, Metabolism and Clinical Chemistry Heidelberg and German Center for Diabetes Research in a message.

The scientists next want to investigate whether RAGE also plays a role in liver and kidney fibrosis and whether treatment with the protein can also remedy this organ damage. The team has already patented the RAGE therapy using modified viruses. (ad)

Author and source information

Video: Current Perspective on Antifibrotic Therapy for Patients with IPF (June 2022).