Why does ALS occur and how is it treated?

June 21st was World ALS Day. What is ALS? The scientific name of ALS is amyotrophic lateral sclerosis (ALS). The principle of this disease is that the motor neurons are damaged, causing the muscles of the limbs, trunk, chest and abdomen to gradually atrophy, and also showing muscle weakness. Finally, the body gradually loses the ability to move, just like being frozen, so it is called ALS. The famous physicist Hawking is one of the people affected by ALS.

ALS is like many progressive (degenerative) diseases. You can see the condition getting worse, but you can't do anything about it. Today, let's talk about the triggering factors and treatment methods of ALS.

01. Predisposing factors of ALS

The current mainstream understanding includes environmental factors, such as the accumulation of neurotoxic substances, which cause the disease.

However, there is now increasing evidence that ALS may be a genetic disease, such as the classic SOD1 mutation. Of course, in addition to this, a series of new mutations have been discovered in recent years. For example, in 2018, the National Institutes of Health (NIH) and the Massachusetts Medical School jointly conducted the largest population genetic study on ALS in history. The study included a total of 125,000 ALS samples. After whole genome sequencing analysis, it was found that in addition to the currently known SOD1 and TDP-43, the gene KIF5A (kinesin family member 5A) was also strongly associated with ALS [1].

There are some mutations in this gene, which will cause the C-terminus of exon 27 of the gene to be disturbed. This disturbance will further affect the skipping of the exon and ultimately affect the gene transcription and translation function. As a result, the function of KIF5A is disturbed and the neural function is affected.

This is the most comprehensive population study on ALS so far, and it also reminds us that rare diseases may be closely related to genes, which is something we should pay attention to in the future.

02. Treatment of ALS

There is actually no cure for ALS at present. However, modern technology is trying to find a way to treat ALS.

For example, there is a gene mutation called superoxide dismutase 1 (SOD1) that is considered to be one of the important pathogenic factors. About 20% of hereditary ALS is caused by this gene mutation. So, for this group of people, gene editing targeting SOD1 may be used for treatment.

Previously, researchers at the University of Illinois at Urbana-Champaign used adeno-associated virus (AAV) vectors to carry the corresponding CRISPR to edit this gene. In mice, the disease was significantly alleviated, the rate of muscle atrophy was reduced, and muscle function was restored to a certain extent. The time from the late stage of the disease to the end of the disease increased by 85%. The rate of muscle atrophy in these mice was reduced, and their muscle function was also improved.

Academician Li Chunyan's team in China also used CRISPR gene editing to treat ALS model mice

The effect is also OK

I think it may be possible to alleviate ALS to a certain extent in the future. Of course, this also requires approval from our country.

Personally, I feel that with the advancement of research, the possibility of special diseases such as ALS going from being completely untreatable to being potentially treatable is increasing.