Genetic Associations With ALS Reversals

Richard Bedlack, MD, PhD, Stewart, Hughes and Wendt Distinguished Professor of ALS at Duke University, discusses a study identifying genetic associations with amyotrophic lateral sclerosis (ALS) reversals.

ALS, also referred to as "Lou Gehrig's disease," is a motor neuron disease which leads to problems with muscle control and movement. There are various types of ALS that are distinguished by early symptoms and, in some cases, genetic causes. Early symptoms may include:

- Muscle twitching
- Cramping
- Stiffness or weakness
- Slurred speech
- Difficulty chewing or swallowing

As the disease progresses, people may become weaker and are eventually wheelchair-dependent. Most people with ALS have a sporadic form of this rare disease. It is believed that these cases are caused by an interaction between genetic and environmental factors. About 10% of all people with ALS have at least one relative with the disease (familial). Familial ALS may be caused by genetic changes in any one of several genes and the pattern of inheritance varies depending on the gene involved.

ALS reversals occur when patients who originally fit the diagnostic criteria for ALS begin to present with sustained clinical improvement of symptoms. A study was conducted to observe the genetic associations with an ALS reversal.

Researchers studied individuals with the ALS reversal phenotype by comparing their whole-genome sequencing data to ALS patients with typically progressive disease. They found two genetic regions of interest, with one significant variant (rs4242007) located in the IGFBP7 gene. This variant is linked to reduced IGFBP7 expression, which may impact the IGF-1 signaling pathway—a possible neuroprotective mechanism in ALS. While the findings are limited by a small sample size, they suggest that targeting the IGF-1 pathway could offer therapeutic potential for ALS.

Chapters:
ALS Untangled 00:00
ALS Reversals 3:31
Genetic Associations With ALS Reversals 6:22
RDCRN Consortium Collaboration 11:53