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New therapeutic approach for incurable nerve disease ALS


Scientists are researching therapeutic approaches to treat ALS

The amyotrophic lateral sclerosis (ALS) nerve disease has been known for over 100 years, but there is still no treatment for it. Scientists are now researching therapeutic approaches against the disease, which many people have known, especially since the so-called "Ice Bucket Challenge".

Incurable nerve disease

The neurodegenerative disease amyotrophic lateral sclerosis (ALS), which can cause violent muscle twitches, muscle weakness and cramps, among other things, leads to the demise of the motor nerve cells and thus to progressive paralysis. The relatively rare disease - around three out of 100,000 people are affected every year - has not yet been curable. Although prominent patients such as the late physics professor Stephen Hawking and the “Ice Bucket Challenge” made ALS better known in summer 2014, the disease, which has been known for around 100 years, is still not curable.

The disease is usually fatal within a short time

In most cases, central nervous system disease results in death within three to five years of onset.

Few people can live with the rare disease like the astrophysicist Steven Hawking for decades.

Scientists from the Technical University (TU) Dresden and colleagues have now found ways to reduce the death of nerve cells and are researching therapeutic approaches for the treatment of ALS.

ALS leads to muscle weakness and paralysis

What actually happens in the body of ALS patients?

As explained in a communication from the TU Dresden, the muscles and thus the movement of the body are controlled by special nerve cells, the motor neurons.

These gradually die in the course of the disease. With the advancement of ALS, patients increasingly suffer from muscle weakness and paralysis, which lead to speech, movement and swallowing disorders and severely impair everyday life.

But which processes lead to the death of the nerve cells? The causes that lead to the death of the nerve cells are not yet fully known.

However, it has been researched that altered behavior of certain proteins is directly related to ALS.

One of them is the RNA-binding protein FUS (FUsed in Sarcoma), which plays a crucial role within the cells: it regulates genetic messengers and influences the interaction of different proteins.

Mutations in the FUS protein lead to deposits and clumping of the FUS protein in the cytoplasm, which creates one of the most aggressive ALS variants.

Death of nerve cells is reduced

Lara Marrone and Jared Sterneckert from the Center for Regenerative Therapies Dresden (CRTD) at the TU Dresden, together with other scientists from Germany, Italy, the Netherlands and the USA, have found that the interactions between the RNA-binding proteins contribute more to the development of ALS disease contribute than was previously known.

In their work recently published in the scientific journal "Acta Neuropathologica", the research team showed that the interactions of damaged FUS proteins with other proteins disturb the balance (homeostasis) of the RNA-binding proteins, which contributes decisively to the degeneration of the nerve cells.

In addition, the scientists showed that a drug-induced breakdown of the cell's own proteins (autophagy) slows down the pathological processes that can be caused by the faulty accumulated FUS protein.

According to the information, the induced autophagy not only saves the RNA-binding proteins, but also reduces the death of the nerve cells.

This improvement was developed by the researchers in cell culture experiments with reprogrammed stem cells (iPS cells) from patients and confirmed in the model organism of the fruit fly.

Protein breakdown machine is affected

"Fusely accumulated FUS protein affects the protein breakdown machine, so FUS accumulates in the cytoplasm of the cells," said Lara Marrone, graduate student at CRTD, and lead author of the study.

"This triggers a vicious cycle that further impedes the cellular quality control systems for proteins that are responsible for maintaining protein balance," says the scientist.

"We therefore suspected that increasing autophagy could also improve the situation of other RNA-binding proteins."

To what extent enhanced autophagy is a possible therapeutic approach for ALS patients, the researchers from the Sterneckert group at CRTD will now investigate.

Another goal of her research is to use RNA-binding proteins in patient samples as biomarkers for ALS disease.

Healing neurodegenerative diseases

Jared Sterneckert and his team use induced pluripotent stem cells (iPS cells) to research neurodegenerative diseases such as ALS and Parkinson's.

They work at the CRTD, where researchers from more than 30 countries decode the principles of cell and tissue regeneration and explore their use for the diagnosis and treatment of diseases.

The CRTD links laboratory and clinic, networks scientists with doctors, uses expertise in stem cell research, genome editing and tissue regeneration for one goal:

The healing of neurodegenerative diseases such as ALS, Alzheimer's and Parkinson's, hematological diseases such as leukemia, metabolic diseases such as diabetes and eye and bone diseases using new diagnostic and therapeutic options. (ad)

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