New therapeutic approach against previously incurable pulmonary fibrosis

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 is not curable. But German researchers are now reporting a possible approach to treating the dangerous lung disease.

Incurable lung disease

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

Pulmonary fibrosis is a chronic disease that causes scarring of the lungs. So far, the disease is not curable. German researchers have now found a possible approach to the treatment of lung disease. (Image: artstudio_pro / fotolia.com)

Body's own protein

The body's own protein RAGE, which has so far mostly been negatively related to chronic inflammation and diabetic sequelae, plays a major role in the repair of DNA damage..

It can obviously also cause the healing of tissue damage as a result of accelerated cell aging.

This has now been discovered by scientists at Heidelberg University Hospital and the German Center for Diabetes Research. The molecular mechanism they describe in the current issue of the journal "Nucleic Acids Research".

Fibrosis has been considered irreversible so far

On the possible therapeutic benefit of the protein they came in mice that can not form RAGE: These develop as a result of limited genome repair pronounced scarring in the lung, a so-called pulmonary fibrosis.

After treatment with the protein, the scarring healed.

"This is amazing in that you have considered fibrosis to be irreversible. With RAGE, we could have found a possible starting point for the healing of these frequent tissue damage for the first time ", says senior author Professor Dr. med. Peter Nawroth, Medical Director of the University Department of Endocrinology, Metabolism and Clinical Chemistry Heidelberg, in a statement.

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

Error-free repair of severe DNA damage

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

The protein plays not only in diabetes but also chronic and excessive inflammatory reactions such as atherosclerosis and sepsis, but also in Alzheimer's disease and carcinogenesis a crucial role.

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

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

In this damage, the two interconnected and twisted strands of genetic information are completely capped, without timely repair, the cell would quickly perish.

Scarred tissue regenerated

Since the DNA in the cells read continuously - it contains the master plan for all processes in the cell - and is claimed, damage is extremely common: in each body cell it comes out mathematically probably several thousand times a day to defects in this vital molecule.

Disruptions in the complex repair mechanisms, for example because the cells are particularly exposed to toxins from the environment or harmful metabolic products, can cause whole tissue associations to rapidly age, degenerate and scar.

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

At present, there are no useful drugs to specifically address disorders of these repair mechanisms, and tissue damage e.g. to prevent diabetes.

Mice that can not form RAGE due to a genetic defect, among others, develop lung fibrosis.

The lung is particularly susceptible to tissue damage because it is in constant contact with the outside world via the respiratory air and is exposed to environmental influences to a great extent.

In the animal model, the researchers were able to elucidate the hitherto unknown molecular mechanism of DNA repair under RAGE involvement and to identify important further protagonists.

By introducing RAGE into the lungs of the mice with the help of modified viruses, not only DNA repair normalized: to the scientists' surprise, the scarred tissue regenerated and regained part of its functional capacity.

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 ever, a molecular therapy for the repair of genetic and cell damage in the lungs and thus for the prevention of fibroses or tumors, which also occur as a result of DNA damage, is within reach," said First author Dr. med. Varum Kumar, University Department of Endocrinology, Metabolism and Clinical Chemistry Heidelberg and German Center for Diabetes Research in a Communication.

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