Biogen Idec and HudsonAlpha Institute for Biotechnology have identified a new gene associated with sporadic amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The associated gene, called TBK1 (TANK-Binding Kinase 1), plays a role inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components).
 
The next-generation genetic sequencing of the exomes (protein-coding portions) of 2,874 ALS patients and 6,405 controls represents the largest number of ALS patients to have been sequenced in a single study to date. While much is known about the genetic underpinnings of familial ALS, only a few genes have been definitively linked to sporadic ALS, which accounts for about 90% of all ALS cases.
 
“These findings demonstrate the power of exome sequencing in the search for rare variants that predispose individuals to disease and that identify potential points of intervention. We are looking at the function of this pathway so that one day this research may benefit the patients living with ALS,” said Tim Harris, Ph.D., D.Sc., senior vice president of technology and translational sciences at Biogen Idec. “The speed with which we were able to identify this pathway and begin our next phase of research shows the potential of novel, focused collaborations with the best academic scientists to advance our understanding of the molecular pathology of disease. This synergy is vital for both the industry and the academic community, especially in the context of precision medicine and whole-genome sequencing.”
 
The researchers are currently using patient-derived, induced pluripotent embryonic stem cells (iPS cells) and mouse models with mutations in TBK1 or OPTN to study ALS disease mechanisms and to screen for drug candidates. Several compounds that affect TBK1 signaling have already been developed for use in cancer, where the gene is thought to play a role in tumor cell survival.