People with rare genetic variants that are linked to Parkinson’s disease and other neurodegenerative disorders have a higher risk for developing amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, new research shows.
The study results were presented at the 149th Annual Meeting of the American Neurological Association, and haven’t been published.
Those with the rare variants have a higher risk for faster ALS progression and also have shorter survival expectancies, the authors said.
“Our findings broaden the understanding of the genetic overlap between ALS and these other disorders by focusing on rare variants instead of common genetic factors,” Maurizio Grassano, MD, lead author of the study and a postdoctoral researcher and neurologist at the University of Turin ALS Center in Italy, said in a statement. “Although identifying these variants may not change treatment, the knowledge can help physicians personalize management of those patients.”
The genetic variants alone don’t necessarily cause ALS, but authors hope this new understanding helps physicians monitor those with higher risks. It also can help families understand potential risks and make informed decisions.
The researchers performed genetic tests for 153 neurodegeneration-associated genes on 791 people with ALS and 757 healthy people without the disease. The team didn’t include people with ALS whose disease could be directly attributed to known genetic mutations for the disease. About 10% of people with ALS have a family history of the disease.
Of those with ALS, 18.3% carried at least one high-impact variant in neurodegenerative genes and 11.4% had a mutation that hadn’t previously been discovered. In those without ALS, 14.4% had a genetic variant while 6.9% had a new mutation.
Overall, the researchers found, those carrying a variant in a neurodegeneration-related gene have a 1.3 times higher risk of developing ALS and a 1.8 times greater risk if the variant was novel or ultra-rare.
The higher percentage of the variants in ALS patients suggests that individuals with ALS have a greater likelihood of carrying genetic mutations associated with other neurodegenerative diseases, which may have increased their risk of developing ALS.
The strongest link was with Parkinson’s disease. People with genes associated with Parkinson’s disease had a 3.6 times greater risk of developing ALS than those without them. After Parkinson’s, the strongest risk for ALS was linked with genetic variants for peripheral neuropathies.
The team didn’t find a higher risk for ALS among those with genetic variants linked to other neurodegenerative diseases like muscular dystrophies or spastic paresis.
The research indicates that ALS and other neurodegenerative diseases may have a common mechanism between them, the authors said.
