Click here to close now.

SYS-CON MEDIA Authors: Liz McMillan, Esmeralda Swartz, Hovhannes Avoyan, Elizabeth White, Adrian Bridgwater

News Feed Item

Two new genes linked to amyotrophic lateral sclerosis (ALS) and related disorders

St. Jude Children's Research Hospital ties mutations in two genes to the death of motor neurons associated with ALS, or Lou Gehrig's disease, and other devastating neurodegenerative problems

MEMPHIS, Tenn., March 3, 2013 /PRNewswire-USNewswire/ -- A study led by St. Jude Children's Research Hospital has discovered mutations in two genes that lead to the death of nerve cells in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, and related degenerative diseases.

The same mutation occurred in both genes and led to the abnormal build-up of the proteins inside cells. These proteins play an essential role in normal RNA functioning and have also been linked to cancer, including the Ewing sarcoma, the second most common type of bone cancer in children and adolescents. The finding is the latest in a series of discoveries suggesting degenerative diseases and cancer may have common origins. RNA is the molecule that directs protein assembly based on instructions carried in DNA.

The study also adds to evidence that seemingly unrelated neurodegenerative diseases may involve similar defects in RNA metabolism. Researchers linked the problems to a specific region of the mutated proteins whose normal function was unclear. The study was published today in the advanced online edition of the scientific journal Nature.

"I hope this study helps to build the foundation for desperately needed treatments for ALS and perhaps a broad range of diseases caused by abnormal RNA metabolism," said J. Paul Taylor, M.D., Ph.D., an associate member of the St. Jude Department of Developmental Neurobiology and senior author of the study. Taylor and James Shorter, Ph.D., an assistant professor in the biochemistry and biophysics department at the University of Pennsylvania's Perelman School of Medicine, are the study's corresponding authors.

Each year approximately 5,600 people in the U.S. are found to have ALS. The disease is nearly always fatal, often within five years. Patients suffer muscle wasting and paralysis that affects their limbs and trunk as well as their ability to talk, swallow and breathe. There is no cure.

For this project, St. Jude sequenced just the portion of the genome called the exome, which carries instructions for making proteins. Researchers sequenced the exomes of two families affected by rare inherited degenerative disorders that target cells in the muscle, bone and brain. Neither family carried mutations previously tied to ALS or related diseases. The project built on the infrastructure developed by the St. Jude Children's Research Hospital -- Washington University Pediatric Cancer Genome Project, which played an important role in finding the mutations.

Researchers found the families carried a single, previously unknown mutation in a pair of RNA-binding proteins named hnRNPA2B1 and hnRNPA1. The proteins both bind RNA and help regulate its function. When researchers checked for the same mutations in 517 ALS patients they found hnRNPA1 protein mutated in two patients. One patient had the inherited form of ALS. The other ALS patient had no family history of the disease.

The new mutations occurred in a region of the proteins Taylor refers to as a prion-like domain because it has similarities with yeast proteins called prions. Prions are proteins that can alternate between shapes as needed for different functions. "Until recently we did not know these domains existed in humans and now we realize that hundreds of human proteins have them," Taylor said. "We're only beginning to understand their function in human cells." 

Researchers showed the prion-like domains are responsible for the shape change that occurs when these proteins convert into slender threads called fibrils. The mutations accelerate fibril formation and recruit normal proteins to form fibrils. This phenomenon called propagation may explain how ALS and related diseases spread throughout the nervous system.

Taylor speculated that the normal function of prion-like domains is to assemble RNAs into temporary structures called granules, which are part of the cell's normal protein production machinery. Granules are normally short lived, and the RNA-binding proteins involved in their formation are recycled. But in cells with hnRNPA2B1 or hnRNPA1 mutation, RNA granules accumulated in the cytoplasm instead of being disassembled. "That's bad news for RNA regulation, which is bad news for those cells," Taylor said.

The study has several important implications, Taylor said. Recognition that the mutations adversely impact regulation of RNA could lead to targeted therapy to correct the problem. The mutation's location in the prion-like domain might also prove significant. Although the mutations in hnRNPA2B1 or hnRNPA1 appear to be rare, hundreds of other RNA-binding proteins have prion-like domains. Taylor said patients with unexplained neurodegenerative diseases may have mutations in these proteins.

The study's first authors are Hong Joo Kim, Nam Chul Kim, Yong-Dong Wang and Jennifer Moore, all of St. Jude; and Emily Scarborough and Zamia Diaz, both of the University of Pennsylvania. The other authors are Kyle MacLea and Eric Ross, both of Colorado State University; Brian Freibaum, Songqing Li, Anderson Kanagaraj and Robert Carter, all of St. Jude; Amandine Molliex, formerly of St. Jude; Kevin Boylan, Aleksandra Wojtas and Rosa Rademakers, all of the Mayo Clinic, Jacksonville, Fla.; Jack Pinkus and Steven Greenberg, both of Brigham and Women's Hospital and Harvard Medical School; John Trojanowski, Bradley Smith, Yun Li and Alice Flynn Ford, all of the University of Pennsylvania; Bryan Traynor, of the National Institute of Aging, National Institutes of Health, Bethesda, Md.; Simon Topp, Athina-Soragia Gkazi, Jack Miller and Christopher Shaw, all of the Institute of Psychiatry, London; Michael Kottlors and Janbernd Kirschner, both of University Children's Hospital Freiburg, Germany; Alan Pestronk and Conrad Weihl, both of the Washington University School of Medicine, St. Louis; Aaron Gitler, Stanford University School of Medicine; Michael Benatar, University of Miami Miller School of Medicine; Oliver King, Boston Biomedical Research Institute, Watertown, Mass.; and Virginia Kimonis, University of California-Irvine.

The research was supported in part by the Packard Foundation, by grants (NS053825, AG032953, DP2OD002177 and NS067354) from the National Institutes of Health, the ALS Association, the Ellison Medical Foundation, a grant (MCB-1023771) from the National Science Foundation and ALSAC.

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other life-threatening diseases. The hospital's research has helped push overall survival rates for childhood cancer from less than 20 percent when the institution opened to almost 80 percent today. It is the first and only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children, and no family ever pays St. Jude for anything. For more information, visit www.stjude.org. Follow us on Twitter @StJudeResearch.

SOURCE St. Jude Children's Research Hospital

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
SYS-CON Events announced today that CommVault has been named “Bronze Sponsor” of SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY, and the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. A singular vision – a belief in a better way to address current and future data management needs – guides CommVault in the development of Singular In...
Temasys has announced senior management additions to its team. Joining are David Holloway as Vice President of Commercial and Nadine Yap as Vice President of Product. Over the past 12 months Temasys has doubled in size as it adds new customers and expands the development of its Skylink platform. Skylink leads the charge to move WebRTC, traditionally seen as a desktop, browser based technology, to become a ubiquitous web communications technology on web and mobile, as well as Internet of Things...
SYS-CON Events announced today that SafeLogic has been named “Bag Sponsor” of SYS-CON's 16th International Cloud Expo® New York, which will take place June 9-11, 2015, at the Javits Center in New York City, NY. SafeLogic provides security products for applications in mobile and server/appliance environments. SafeLogic’s flagship product CryptoComply is a FIPS 140-2 validated cryptographic engine designed to secure data on servers, workstations, appliances, mobile devices, and in the Cloud....
SYS-CON Events announced today that FierceDevOps will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. FierceDevOps keeps software developers and IT operations personnel updated on the latest news and trends around the rapidly evolving role of the traditional IT worker.
SYS-CON Events announced today that StorPool Storage will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. StorPool is distributed storage software that allows service providers, enterprises and other cloud builders to run data storage on standard x86 servers, instead of using expensive and inefficient storage arrays (SAN).
SOASTA, the leader in performance analytics, today reported record growth of the CloudTest community, exceeding 30,000 registered users of the CloudTest platform in Q1 2015. SOASTA also announced widespread adoption of its Web and mobile testing solutions, with more than 1,600 customers completing more than 285,000 tests using CloudTest during the quarter. This rapid growth shows that DevOps-driven digital businesses are embracing a more continuous approach to testing, and CloudTest is meeting t...
SYS-CON Events announced today that QTS Realty Trust, one of the nation’s largest and fastest-growing providers of data center facilities and cloud services and a leader in security and compliance, will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. QTS Realty Trust, Inc. (NYSE: QTS) is a leading national provider of data center solutions and fully managed services, and a leader in security and compliance...
ProfitBricks, the provider of painless cloud infrastructure for IaaS, today announced the release of a Node.js SDK written against its recently launched REST API. This new JavaScript based library provides coverage for all existing ProfitBricks REST API functions. With additional libraries set to release this month, ProfitBricks continues to prove its dedication to the DevOps community and commitment to making cloud migrations and cloud management painless. Node.js is an open source, cross-pl...
Today, IT is not just a cost center. IT is an enabler and driver of business. With the emergence of the hybrid cloud paradigm, IT now has increasingly more capabilities to create new strategic opportunities for a business. Hybrid cloud allows an organization to utilize multi-tenant public clouds, dedicated private clouds, bare metal hosting, and the associated support and services for the right use cases through an on-demand, XaaS model. This model of IT creates tremendous opportunities for busi...
GENBAND has announced that SageNet is leveraging the Nuvia platform to deliver Unified Communications as a Service (UCaaS) to its large base of retail and enterprise customers. Nuvia’s cloud-based solution provides SageNet’s customers with a full suite of business communications and collaboration tools. Two large national SageNet retail customers have recently signed up to deploy the Nuvia platform and the company will continue to sell the service to new and existing customers. Nuvia’s capabili...
SYS-CON Events announced today that IndependenceIT, a leading software provider of simplified IT management solutions for workspaces, applications and desktops-as-a-service, will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. IndependenceIT's Cloud Workspace® Suite combines application, end-user and infrastructure management into a seamless, easy-to-manage platform, with a unified management interface an...
SYS-CON Events announced today that that Innodisk, the service-driven provider of industrial embedded flash and DRAM storage products and technologies, will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. Innodisk is a service-driven provider of industrial embedded flash and DRAM storage products and technologies. With satisfied customers across the embedded, aerospace and defense, cloud storage markets an...
Sonus Networks introduced the Sonus WebRTC Services Solution, a virtualized Web Real-Time Communications (WebRTC) offer, purpose-built for the Cloud. The WebRTC Services Solution provides signaling from WebRTC-to-WebRTC applications and interworking from WebRTC-to-Session Initiation Protocol (SIP), delivering advanced real-time communications capabilities on mobile applications and on websites, which are accessible via a browser.
SYS-CON Events announced today that WSM International (WSM), the world’s leading cloud and server migration services provider, will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. WSM is a solutions integrator with a core focus on cloud and server migration, transformation and DevOps services.
SYS-CON Events announced today that Site24x7, the cloud infrastructure monitoring service, will exhibit at SYS-CON's 16th International Cloud Expo®, which will take place on June 9-11, 2015, at the Javits Center in New York City, NY. Site24x7 is a cloud infrastructure monitoring service that helps monitor the uptime and performance of websites, online applications, servers, mobile websites and custom APIs. The monitoring is done from 50+ locations across the world and from various wireless carr...