Biomarker for ALS: DZNE participates in international project

Researchers at DZNE’s Ulm site are involved in an international project on the neurological disease amyotrophic lateral sclerosis (ALS), which is associated with severe muscle paralysis and ultimately leads to death. The US-based foundation Target ALS is funding DZNE’s contribution to this endeavor with around 200,000 US dollars. The objective is to facilitate the diagnosis of ALS by analyzing genetic material (DNA) from the blood. Specifically, the scientists aim to assess certain characteristics – so-called epigenetic signatures – of these DNA molecules. The project partners are Ulm University Hospital, the University of California, Irvine, and the US company “Twist Bioscience Corporation”.

“There is a need for methods to diagnose ALS reliably and at an early stage,” says Prof. Karin Danzer, research group leader at DZNE’s Ulm site. “On the one hand, to enable a timely diagnosis. And on the other hand, to be able to include patients in clinical studies at an early stage. There is currently no cure for ALS, which is why clinical studies are key to developing better treatments. However, if the disease has already progressed too far due to late diagnosis, participation in clinical studies is no longer possible. In such cases, there is too much damage to the nervous system and the therapeutic window has already closed.”

Damaged neurons

Diagnosing ALS can be a lengthy process. This is partly because the symptoms of ALS, such as muscle weakness, twitching or stiffness, can be subtle at first and may also occur in other diseases. Currently, the biomarker “neurofilament light chain” (NfL) is used to confirm the diagnosis. NfL is a protein that is released when neurons are damaged and can be detected in the blood or cerebrospinal fluid. NfL levels are significantly higher in people with ALS than in healthy individuals and in patients with other neurodegenerative diseases. The aim of the current project is to identify an additional biomarker that ideally sounds the alarm before neuronal damage occurs.

Molecular signatures

Thus, Dr. Sebastian Michels from Ulm University Hospital and the team led by Karin Danzer are focusing on genetic material. “We are looking at DNA molecules present in the blood. Specifically, we are targeting methyl groups attached to the DNA. These chemical tags, also known as epigenetic signatures, influence which parts of the genome are active. That is, they switch individual genes on or off, so to speak. In individuals with ALS, this gene expression is different from that of healthy people. We want to determine whether these changes are so characteristic, like a fingerprint, that they can be used to reliably identify ALS.”

To this end, blood samples from a total of 500 individuals – with ALS and (for comparison) also from healthy persons – will be analyzed. For this, the researchers will make use of machine learning, i.e. artificial intelligence. The project is planned for two years. “Our goal is to find a distinct epigenetic signature. Based on such a biomarker, one could then develop a blood test specific for ALS,” says Danzer.

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