Researchers announced the first-ever evidence-based description of the neuronal protein clumps thought to be important in Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, a fatal neurodegenerative condition.

The study, published online today in Proceedings of the National Academy of Sciences, also provides the first definitive evidence that these protein clumps are indeed toxic to the type of neurons that die in patients with ALS.

The study focuses on a subset of ALS cases - an estimated 1 to 2 percent - that are associated with variations in a protein known as SOD1. However, even in patients without mutations in their SOD1 gene, this protein has been shown to form potentially toxic clumps. The researchers discovered that the protein forms temporary clumps of three, known as a "trimer," and that these clumps are capable of killing motor neuron-like cells grown in the laboratory.

Until now, researchers did not know what these fleeting clumps looked like or how they might affect cells.

Once the trimers' structure was established, the team spent several more years developing methods to test the trimers' effects on motor neuron-like cells grown in the laboratory. The results were clear: SOD1 proteins that were tightly bound into trimers were lethal to the motor neuron-like cells, while non-clumped SOD1 proteins were not.
The team plans to further investigate the "glue" that holds the trimers together in order to find drugs that could break them apart or keep them from forming.

In addition, these findings could help shed light on other neurodegenerative diseases, such as Alzheimer's disease and Parkinson's.

http://news.unchealthcare.org/news/2015/december/new-study-opens-new-door-for-als-drug-discovery