Cells signal the development of ALS long before symptoms occur

The core of the problem lies in mitochondria – small “power plants” inside cells. They are the first to signal distress. Their work and delivery to those parts of neurons where energy is especially needed – for example, in the long branches that transmit impulses to muscles – is disturbed.

Using advanced CRISPR DNA editing technology and reprogrammed stem cells, the scientists created a model of the disease. They introduced various mutations that cause ALS into human cells and then “grew” two types of neurons from them – disease-prone motoneurons and more resistant interneurons.

Further analysis using single cell sequencing technology allowed us to look inside each cell and understand how it works. It turned out that it was the motoneurons that were the first to show changes, with failures affecting the same regions regardless of the specific mutation. This suggests that there is a single vulnerable mechanism that can be attempted to be blocked by drugs.

Until recently, it was thought that the development of ALS began with the misplacement of certain proteins in the cell. However, now it turns out that the problem is deeper – new toxic properties that these proteins acquire and trigger a chain of disorders.

Another alarming point is the dramatic deterioration of mitochondrial transport to areas where they are especially needed. Without a stable supply of energy neurons lose the ability to interact with other cells, which accelerates the destruction of the nervous system.

According to the researchers, the challenge now is to understand exactly how these early failures originate and how they destroy the connections between neurons and muscles. The answers to these questions could form the basis of new application points for ALS treatment – especially when it comes to the very beginning of the disease, when symptoms have not yet manifested.