Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is thought to have a significant link to genetics. As this disease progresses, neurons stop functioning properly, leading to the loss of many bodily functions over time. Although changes in several genes have been associated with an increased risk of developing ALS, scientists suspect that we still have to find many of the more rare genetic variations that are connected to the disease. Researchers are hopeful that a more comprehensive understanding of ALS will improve treatment options.
There is one approved treatment for ALS cases that are linked to changes in a gene called SOD1, and more advancements like that could be made in the future when we know more. An ALS patient’s genetic data can offer insight into how their disease will progress. Genetic variants linked to the disease can also inform people who want to have children.
Scientists have now found more rare, genetic variants that are linked to ALS. In a study published in Nature Genetics, researchers analyzed genetic data from over 18,000 ALS patients and tens of thousands of unaffected individuals to look for small changes in gene sequences that can increase ALS risk. The sheer size of this dataset enabled researchers to reveal very rare genetic variants that may have a small contribution or only be found in a few people.
This work confirmed that certain previously identified genes are linked to ALS, such as SOD1, KIF5A, and TBK1. It also found novel ALS-linked variants in HTR3C, YKT6, GBGT1, CAPN2, and KNTC1. This work brings the number of ALS cases that are connected to a genetic cause from 20% to 25%.
Now scientists can use this new data in the search for improved ALS therapeutics. Since only about 2% of ALS patients have a case that has been linked to SOD1, there are very few treatment options for the vast majority of patients. This work can offer new insights, however.
"This study appreciably increases our knowledge of what causes [ALS}, showing that it has a significant genetic component in about a quarter of people with the disease, regardless of family history. That means everyone presenting with symptoms should be offered genetic testing, and this increased knowledge improves the chances of developing an effective treatment," explained senior study author Ammar Al-Chalabi, Professor of Neurology and Complex Disease Genetics at King's College London, among other appointments.
Sources: King’s College London, Nature Genetics
