What is MND/ALS?
Motor Neurone Disease (MND) is a disease that gradually stops the brain from being able to send movement signals to the muscles. The most common type is Amyotrophic Lateral Sclerosis (ALS).
It affects two sets of nerve cells: the ones in the brain, and the ones in the spinal cord. As those nerve cells die, the messages from the brain can no longer get through to the muscles. Without instructions from the brain, the muscles don't know what to do. Over time, they weaken and shrink, a process doctors call 'wasting'.
. It isn't that the muscles themselves are the problem. They're just not receiving the signals they need to function.
how does movement work?
Every time you do something physical (pick up a cup, take a step, take a breath) your brain sends an electrical message down through your spinal cord and out to your muscles.
Think of it like a telephone call. Your brain is the person making the call, your spinal cord is the phone line, and your muscles are the person picking up at the other end.
The "telephone wires" in this system are your nerve cells, which scientists call motor neurons. There are two kinds working together. The first type sits in the brain and sends the message downward. The second type picks it up in the spinal cord and passes it directly to the muscle. Both types need to be working properly for you to move.
In a healthy body, this happens in a split second, without you even thinking about it. In ALS, this system starts to break down.
Why do nerve cells die?
This is the question researchers have been working hardest to answer.
The honest answer is: several things go wrong at once, and they often make each other worse. Here, we'll list them one by one.
1. The cell gets flooded with too much of a good thing
Your nerve cells use a chemical called glutamate to send signals to each other. Think of glutamate like electricity: you need it to make things work, but too much can blow a fuse.
In ALS, glutamate builds up to levels that are far too high. This over-stimulates the nerve cells, flooding them with calcium and essentially burning them out from the inside. This process is called excitotoxicity. "Excito" refers to the cell being over-excited; "toxicity" because that excitement becomes poisonous.
One of the first ALS drugs ever approved, riluzole, works by trying to reduce this build-up of glutamate.
Why do nerve cells die?
2. Proteins that should be helpful start to clump up
Inside every cell, there are proteins doing important jobs. In ALS, one protein in particular, called TDP-43 (TAR DNA-binding protein 43), starts to misbehave.
Normally it lives in the cell's control centre (the nucleus) and helps manage how the cell reads its own genetic instructions. In ALS, TDP-43 wanders out of the nucleus and starts forming sticky clumps in the wrong part of the cell.
These clumps are found in the nerve cells of over 97% of people with ALS. They gum up the cell's normal workings and, over time, kill it.
You can think of it like a factory where the manager has abandoned their post and started blocking the corridor instead. Nothing can get done, and eventually the whole factory shuts down.
Why do nerve cells die?
3. The cell's power supply fails
Every cell in your body has tiny power generators called mitochondria. They take in fuel (from the food you eat) and turn it into energy the cell can use.
Motor neurons need a huge amount of energy. They're some of the longest cells in the body. A single nerve cell can stretch from your spinal cord all the way down to your foot, and can contain up to 2 million mitochondria.
In ALS, the mitochondria in these cells start to malfunction. They produce less energy and more waste products. It's like a car engine that's running rough: guzzling fuel, not going far, and giving off too much exhaust.
An energy-starved nerve cell can't do its job, and eventually it dies.
Why do nerve cells die?
4. The brain's support cells turn against the neurons
Your brain isn't made up of neurons alone. There are also "support cells" whose job is to look after the neurons: feeding them, cleaning up waste, and protecting them from harm. Two types of these support cells are called astrocytes and microglia.
In a healthy brain, these cells are incredibly helpful. But in ALS, something goes wrong. They shift from being nurturing and protective to actually releasing substances that are toxic to the very neurons they're supposed to be looking after.
Scientists don't fully understand why this happens, but it appears to significantly accelerate the loss of motor neurons.
current research
Switching off faulty genes
In some families, ALS is caused by a faulty gene that gets passed down through generations. Scientists have developed treatments called antisense oligonucleotides (or ASOs) that can essentially "switch off" a faulty gene before it causes damage. The first of these, targeting a gene called SOD1, is now approved and has shown real promise in clinical trials.
Targeting the TDP-43 protein clumps
Because TDP-43 clumping is present in almost all ALS cases, it's a major target for new drugs. Several research teams are working on ways to either stop the clumping from happening in the first place, or help the cell clear the clumps away before they cause damage.
Finding the disease earlier
A simple blood test that measures a protein called neurofilament light chain (NfL) is showing great promise as an early warning sign of nerve cell damage. If doctors can spot ALS earlier, before too many neurons are lost, future treatments will have a much better chance of working.
