Gene Associated with Parkinson's and Alzheimer's Linked to ALS

A genetic mutation that has previously been linked to Parkinson’s disease and Alzheimer’s disease could also be connected to amyotrophic lateral sclerosis (ALS), according to a team of researchers supported by the National Institute of Health (NIH).

The research was led by Bryan Traynor, M.D., Ph.D., of the Intramural Research Program of the National Institute on Aging (NIA) at the NIH and John Landers, Ph.D., of the University of Massachusetts Medical School, Worcester, with genetic data collected by teams of scientists around the world who were dedicated to the project.

The data, published in the March 21, 2018 issue of Neuron, was collected from a large-scale genome-wide association study conducted by the NIH team while the University of Massachusetts group zeroed in on the analyzation of rare variants in next generation sequence data. In all, over 125,000 samples were evaluated, making this the largest such study of ALS performed to date.

With key funding support from the NIA, the National Institute of Neurological Disorders and Stroke (NINDS) at NIH, and other public and private sector organizations, it was found that mutations in kinesin family member 5A (KIF5A) can disrupt transport of key proteins up and down long, threadlike axons that connect nerve cells between the brain and the spine, eventually leading to the neuromuscular symptoms of ALS.

KIF5A normalizes proteins from the kinesin family that serve as small, intracellular motors. Issues with these proteins are frequently connected to neurodegenerative diseases with muscle weakening, stiffening, and spasticity symptoms. Most people with ALS become paralyzed or die within 5 years of diagnosis, however, patients found to have the KIF5A mutation are exhibiting a longer survival period of about 10 years.

In the official statement released by the NIH, Richard J. Hodes, M.D., director of NIA, said: “The extraordinary teamwork that went into this study underlines the value of global, collaborative science as we seek to better understand devastating diseases like ALS,” said “These types of collaborative data collection and analysis are important in identifying the pathways underlying disease and in developing approaches to treatment and prevention.”

While the discovery advances scientists’ knowledge of what causes the neurodegenerative disease, it’s still new, and more research is required before concrete conclusions can be made. Next steps likely include further study of the frequency and location of mutations within the KIF5A and determining what cargos are being disrupted.

Dr Traynor and his team hope that today’s news will assist in the finding of what aspect of axonal transport is imperative to maintaining the cell: “While this is unlikely to be a very common genetic cause for ALS, it identifies important new directions to explore possible future gene therapies.”