Amyotrophic Lateral Sclerosis

Propelling breakthroughs in amyotrophic lateral sclerosis (ALS) research

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder that damages nerve cells in the brain and spinal cord. It causes muscle weakening that worsens over time and eventually leads to difficulties with movement, eating, speech and breathing.

About 10% of ALS cases are familial, meaning they are linked to genetic changes passed down through families. The remaining 90% of cases are considered sporadic, and likely are caused by a mix of genetic and environmental factors.

There is no cure for ALS and treatment options are limited. Our scientists pursue breakthroughs to improve ALS treatment by:

• Investigating the C9ORF72 repeat expansion, the most common genetic cause of ALS
• Studying how genetics, epigenetics and cell-to-cell interactions influence movement-related and cognitive symptoms in ALS
• Leveraging induced pluripotent stem cells (iPSCs) to study how ALS develops and evaluate potential new therapies

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What do ALS researchers at VAI study?

Scientists at VAI investigate how ALS begins and progresses with the goal of identifying new, more effective treatments.

Investigating the C9ORF72 repeat expansion, the most common genetic ALS cause

C9ORF72 is a gene that helps cells remove and recycle waste. In some people, part of this gene contains an incorrectly repeated DNA sequence. This “repeat expansion” disrupts normal cell function and results in a harmful buildup of toxic proteins and debris.

Over time, this damage leads to the death of cells that control muscle movement, causing the progressive muscle weakening seen in ALS. Repeats in C9ORF72 are the most common cause of genetic ALS. The C9ORF72 repeat expansion also influences sporadic ALS, which occurs in people without a family history.

VAI scientists study how the C9ORF72 repeat expansion contributes to both inherited and non-inherited ALS, with the goal of developing improved therapies that target this critical gene variant. This research also may help us understand other diseases linked to C9ORF72, such as frontotemporal dementia.

Studying how genetics, epigenetics and cell-to-cell interactions influence movement-related and cognitive symptoms in ALS

An estimated 90% of ALS cases are sporadic, meaning there is no family history of the disease. Research suggests that these cases likely arise from a mix of factors, including genetics, interactions between cells, and epigenetics, which regulate how and when the instructions in genes are used.

Developing new ways to treat ALS requires an in-depth understanding of all the factors that contribute to the disease. VAI scientists investigate these interconnected mechanisms with the goal of designing more effective treatments and identifying biomarkers to improve diagnosis and disease monitoring.   

Leveraging induced pluripotent stem cells (iPSCs) to study how ALS develops and evaluate potential new therapies

Induced pluripotent stem cells (iPSCs) are derived from mature cells, such as those from the blood or skin, that are “reprogrammed” in the lab to return to an earlier, blank-slate state. From there, they can be transformed into other types of cells, such as brain cells, making them powerful tools for studying diseases like ALS.

VAI scientists use iPSCs to create human brain cells and “mini brains” in petri dishes that enable detailed study of how ALS impacts cells and testing of potential new therapies in the lab.