This Critical Discovery Gets Us Closer the Cause and Treatment of ALS

BIG NEWS in the ALS community this week. As reported by NewsWise, researchers at the Mayo Clinic and St. Judes Children’s Research Hospital have discovered the dysfunctional cellular mechanism behind Amyotrophic Lateral Scerlosis (ALS) or Lou Gehrig’s disease.

This error also applies to a form of dementia that some ALS patients have, and possibly applies to Alzheimer’s disease.

What scientists found: a mutation in that produces an abnormal “building block” protein (T1A1) that is critical in the assembly of membrane-less organelles (i.e. a process called phase separation), the latter being necessary for orderly cell function. The abnormal protein accumulates in the organelles and subsequently kills off muscle-controlling neurons.

How they found it: They observed the genetics of families affected by ALS and traced it to the T1A1 mutation, which is carried by people who have the disease. They then analyzed brains of deceased ALS patients, and discovered a build-up of organelles with T1A1 called stress granules in the actual neurons. The granules also contained the TDP-43 protein, which has been indicated to also in-part cause ALS when abnormal. Finally, when tested in tubes, it was discovered that the T1A1 mutation caused the delay of the normal stress granule assembly, thus “trapping” TDP-43.

What it means: For those suffering from ALS, a specific type of dementia associated with ALS called frontotemporal dementia (FTD), and other neurodegenerative diseases, this discovery can change the direction of treatment development. Right now, treatments aren’t super effective and typically target the already damaged neurons. Now, drug developers know to target treatment that prevents the degeneration of neurons through supporting the proper phase separation of cells.

What’s next for research?: Scientists now want to learn more about phase transition and stress granule regulation to further develop better therapies for those suffering from neurodegenerative diseases.

To read more about this ALS discovery, check out NewsWise and the original study in Neuron here.