'Ice Bucket Challenge' Helps Find New ALS-Related Gene

Deborah Brauser

July 29, 2016

Two summers ago, social media streams were filled with video after video of individuals dumping cold water over themselves in order to increase awareness and garner donations for amyotrophic lateral sclerosis (ALS). Now, new research is crediting part of the $115 million raised to helping to identify NEK1 as a new ALS-related gene.

In a chart released last year, the ALS Association showed that $77 million of the proceeds from its ubiquitous "Ice Bucket Challenge" went to various research projects. This included establishing the US arm of the global gene sequencing Project MinE under John Landers, PhD, University of Massachusetts Medical School, Worcester.

The new discovery occurred after Dr Landers' group worked with MinE researchers from around the world to search for ALS risk genes in more than 1000 familial cases.

In further analyses of more than 13,000 individuals, NEK1 variants were found in significantly more patients with ALS than in a group of their healthy peers.

"NEK1 is known to have multiple roles in neurons, including maintenance of the cytoskeleton that gives the neuron its shape and promotes transport," notes the ALS Association in a release. "Disruption of these cellular functions…has been linked to increased risk of ALS."

In the same release, Dr Landers said that donations from the ALS Ice Bucket Challenge led to the global collaboration among scientists, which made "this important discovery" possible.

"It is a prime example of the success that can come from the combined efforts of so many people," he said. "This kind of collaborative study is, more and more, where the field is headed."

The study findings were published online July 25 in Nature Genetics.

Largest Study of Its Kind

The ALS Association notes that this is the largest study ever conducted of familial ALS and included 80 researchers from 11 countries.

The first part of the study included 1376 patients with familial ALS and 13,883 healthy controls. Here, the NEK1 p.Arg261His variant was identified as a possible risk factor for ALS in "an isolated community in the Netherlands," report the investigators.

Replication analysis of 10,589 samples showed "significant disease association" for the p.Arg261His variant, and assessment of 3362 samples showed disease association for other NEK1 loss-of-function variants.

"In total, we observed NEK1 risk variants in nearly 3% of ALS cases," the researchers write. "Our results provide new and important insights into ALS etiopathogenesis and genetic etiology."

The ALS Association notes that it is now funding the development of mouse models to better understand how NEK1 contributes to the disease process. As soon as they're generated, these models will be released to the full research community.

"These tools are important for ALS drug development," the organization stressed.

The study authors have disclosed no relevant financial relationships.

Nature Genet. Published online July 25, 2016. Article

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