Breakthrough prevention hope for motor neurone illness: Scientists pinpoint potential trigger

Scientists could be on the verge of a medical breakthrough in understanding what is driving cases of amyotrophic lateral sclerosis (ALS)—the most common form of motor neurone disease. 

The exact cause of ALS has long been unknown.

But some research suggests it could be down to a complex interplay of genetic, environmental, and possibly lifestyle factors—often hitting seemingly fit and healthy people. 

Now, US scientists have discovered that ALS could instead by an autoimmune disease—when the immune system mistakenly identifies healthy cells and tissues as foreign invaders and attacks them, leading to inflammation and damage.

They found that certain white blood cells, called CD4+ T cells, mistakenly target certain proteins that are part of the nervous system in people with ALS.

Experts today claimed the findings were the first-of-its-kind and could pave the way for new more effective treatments. 

ALS claimed the life of Sandra Bullock’s partner Bryan Randall in 2023 and the acclaimed scientist Stephen Hawking famously suffered from it.

The muscle wasting condition progressively damages parts of the nervous system and is incurable. It gradually stops patients being able to move, talk and even eat. 

Researchers found that certain white blood cells, called CD4+ T cells, mistakenly target certain proteins that are part of the nervous system in people with ALS

Dr Alessandro Sette, an expert in immune response and inflammation at La Jolla Institute for Immunology in San Diego and study co-author said: ‘This is the first study to clearly demonstrate that in people with ALS, there is an autoimmune reaction that targets specific proteins associated with the disease.’ 

Professor David Sulzer, an expert in psychiatry, neurology and pharmacology at Columbia University and study co-author, added: ‘There is an autoimmune component to ALS, and this study gives us clues as to why the disease progresses so rapidly. 

‘This research also gives us a possible direction for disease treatment.’ 

Along with twitches, cramps and muscle weakness are among the early signs of the condition, along with slurred speech and weight loss.

There is currently no cure but doctors can provide treatments to help reduce the impact it has on a person’s life.

In the fresh study, researchers tracked how ALS patients’ T cells—a type of white blood cell that develops in the thymus and matures to fight infection—responded over time. 

The scientists found two distinct responses, based on their predicted survival times.

Those with shorter predicted survival times saw their inflammatory CD4+ T cells, often called helper T cells, quick to release molecules that fight infection when they recognised certain harmful proteins. 

ALS can lead to paralysis and eventually death. The acclaimed scientist Stephen Hawking famously suffered from it

The second group, which had ‘significantly longer projected survival times’, also had higher numbers of different T cells, anti-inflammatory CD4+ T cells, the researchers said. 

Anti-inflammatory CD4+ T cells are important because they can regulate disease. 

When the immune system fights a viral infection, for example, it churns out inflammatory T cells to eliminate the infected cells. 

Once the immune system clears the virus, anti-inflammatory CD4+ T cells step in to prevent other T cells from damaging healthy tissues.

Writing in the journal Nature, the researchers said a ‘protective T-cell response was strongest in people with longer predicted survival times’. 

The findings suggest that CD4+ T cells ‘may reduce harmful autoimmune responses and slow the progression of ALS’, they added.

Tanner Michaelis, a research technician at La Jolla Institute for Immunology and study co-author, said: ‘Hopefully, now that we know the specific target for these immune cells, we can make more effective therapies for ALS.’

Dr Sette also added: ‘There are several neurodegenerative diseases where we now have clear evidence of immune cell involvement.

ALS also claimed the life of Sandra Bullock’s partner Bryan Randall (pictured with Sandra in 2018) in 2023

‘This approach may be applicable for additional disorders such as Parkinson’s, Huntington’s, and Alzheimer’s.’ 

Around 5,000 adults in the UK have ALS and there is a one in 300 risk of developing the condition over the course of a person’s life.

Life expectancy for about half of those with the condition is between just two and five years from the onset of symptoms. But these can worsen rapidly.

Some people may live for up to 10 years, and, in rarer circumstances, even longer. 

Locked-in syndrome (LIS) is a rare neurological disorder that can also occur in some progressive cases of ALS.