We now have an unprecedented deep understanding of the disease and the disease mechanisms which creates an opportunity to realize real treatment breakthroughs.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease impacting nerve cells in the brain and spinal cord, reducing muscle function and control. ALS can be traced to mutations in more than 25 different genes and is often caused by a combination of multiple sub-forms of the condition. Cases usually cannot be predicted, although a small percentage are inherited. ALS has a devastating impact on patients and families. ALS patients’ average life expectancy is three years; after diagnosis patients only have two years to live. There is currently no cure for the disease.

The QurAlis team together with others in the field cracked the code on sporadic ALS through the identification of major disease drivers linked to TDP-43 pathology. Using human neuronal stem cell models from ALS patients, QurAlis co-founder and Harvard professor Kevin Eggan, PhD, discovered in 2019 that the expression of STATHMIN-2 (STMN2) is regulated by TDP-43. The Eggan Lab showed that loss of normal TDP-43 function leads to a highly significant decrease in expression of STMN2 and an impairment in neuronal repair which could be rescued by restoring STMN2 levels. These results were published in Nature Neuroscience.

In addition to nearly all ALS patients, TDP-43 pathology is also associated with approximately 50 percent of patients with frontotemporal degeneration (FTD), the second most common form of dementia; about a third of Alzheimer’s Disease patients; and up to seven percent of Parkinson’s disease patients.