A new study provides the first evidence-based description of a type of protein clump thought to play an important role in ALS, or Lou Gehrig’s disease, by killing the nerve cells that control movement.

Share on Pinterest The researchers found trimers of tightly bound SOD1 protein were deadly to motor neuron-like cells, while non-clumped SOD1 protein was not.

Writing in the Proceedings of the National Academy of Sciences, the team from the University of North Carolina at Chapel Hill also explain how theirs is the first evidence that the protein clumps are toxic to motor neurons – the type of nerve cells that die in patients with ALS.

Senior author Nikolay Dokholyan, a professor of biochemistry and biophysics, says:

“This study is a big breakthrough because it sheds light on the origin of motor neuron death and could be very important for drug discovery.”

Amyotrophic lateral sclerosis (ALS) is a group of diseases that gradually destroy motor neurons – the nerve cells that control muscle movement. It first came to public attention when the American baseball player Lou Gehrig died of the disease in 1941.

Patients with ALS suffer gradual paralysis and early death as their motor neurons die off and they lose their ability to move, speak, swallow and breathe.

The study concerns a subset of ALS that affects around 1-2% of patients. Patients in this type of ALS have variations in a protein called SOD1. However, the researchers note that toxic SOD1 protein clumps can also form in patients without the mutated form.

In their study, the team found SOD1 first collects into clumps of three protein molecules, or “trimers.” When they tested them, they found the trimers could kill lab-grown cells similar to motor neurons.