Big Data Analytics, Genomics to Spur Collaborative ALS Research
September 09, 2015 – Three major academic medical centers are combining their big data analytics forces to tackle Amyotrophic Lateral Sclerosis, a common yet poorly understood degenerative neuromuscular condition. Johns Hopkins University’s Robert Packard Center for ALS Research, Cedars-Sinai Medical Center’s Regenerative Medicine Institute and the Massachusetts General Hospital Neurological Clinical Research Institute will coordinate research efforts to uncover the root causes of ALS, utilizing advances in genomics, precision medicine, machine learning, and pharmaceutical developments to work towards a cure for the fatal disease. The project, called Answer ALS, represents “An unprecedented approach to understanding and defeating disease,” said Dr. Jeffrey Rothstein, Director of the Brain Science Institute and the Robert Packard Center for ALS Research at Johns Hopkins University and the Executive Director of Answer ALS. While ALS research has drawn massive international attention in the past few years after social media prompted the uptake of the Ice Bucket Challenge as a way to bring funding to non-profit research organizations, clinicians currently have few treatment options for patients diagnosed with the disease. “This project will bring together world-renowned ALS research scientists to work against an aggressive timeline for understanding, treating and eventually finding a cure for this disease,” Rothstein continued. “The substantial initial funding from these generous supporters is a critical step forward in our effort to provide hope to those affected by ALS.”. Researchers will develop a centralized foundation of clinical and genetic data that will underpin cross-organizational research targeted at discovering the origins and pathways of the disease. The organizations hope to more clearly define the condition’s subtypes and methods of development as a first step towards developing new clinical trials that may produce personalized treatments. “We are combining big data, comprehensive biological analytics, technology and science in a way that would not have been possible a decade ago,” said Clive Svendsen, PhD, Director of the Regenerative Medicine Institute at Cedars-Sinai Medical Center and Co-Director of Answer ALS. “What is so exciting and important is that all of this data will be made publicly available with free, open access to the ALS research community, so that we can make faster and greater strides together to find a cure for this disease.” “By leveraging clinical and sample data collection systems built by the Northeast ALS Consortium with the support of the ALS Association and ALS Finding a Cure Foundation, enrollment of participants and sharing of data and samples will be accelerated,” added Merit Cudkowicz, MD, Chief of Neurology and Co-Director of the Neurological Clinical Research Institute at Massachusetts General Hospital and Co-Director of Answer ALS. The project will collect longitudinal clinical data on at least 1000 ALS patients, and will also examine brain cells of affected patients using advanced genomics and robotic imaging analytics. The coalition has already raised $20 million in funding to support its mission, backed by stakeholders including the National Football League, PGA TOUR, and ALS Finding a Cure. “To accelerate development of treatments for people with ALS, we brought together a remarkable team of scientists, a true powerhouse, to answer one of the hardest and most important questions in the biology of ALS,” said Peter Foss, President of the ALS Finding a Cure Foundation, and General Manager of the GE/NFL TBI research project. “We support open, collaborative science that tackles fundamental therapy-driven questions and includes real-time community sharing of data. This is the best approach to accelerate finding a cure for all people with ALS.”.
What Causes ALS? With Robert Kalb, MD: Research: Feinberg School of Medicine: Northwestern University
Robert Kalb, MD, Director of the Les Turner ALS Center at Northwestern Medicine, is optimistic that more breakthroughs in the basic biology of the disease are on the way and a cure is possible. Robert Kalb, MD, details how someone is diagnosed with ALS why they come to Northwestern for treatment. Robert Kalb: “ALS is a clinical diagnosis. There is no test, there’s no blood test. There are. no imaging tests. There’s no electrophysiologic test that makes the diagnosis. It’s a constellation of signs and symptoms. Once a person gets to our clinic, and we assemble all of the pieces of information, and include the positive and the negative results, we’re pretty confident that if a person has ALS, that we can give them that diagnosis. And then once they are enrolled in the ALS clinic, they can get a variety of services and support through the Les Turner Center.” Robert Kalb: “We think that a major problem in ALS is the recognition of damaged proteins and disposal of them. And because this disposal process, or the recognition and the disposal process, is impaired, what ends up happening is an accumulation of damaged proteins and cells don’t like that. Cells are very unhappy when misfolded damaged proteins accumulate.” Currently, part of the research in Kalb’s lab is focusing on making a drug for treating patients and also working on different aspects of ALS. Robert Kalb: “I think everybody in the clinic or the physicians, Senda Driss and Mike Li and Teepu Siddique and myself and Robert Sufit, I think we’re all very committed to taking care of the patients and going long hanging in there and willingness to see it through to the end and that’s my goal is to get to the end, to put myself out of business.” I’m the division chief for neuromuscular medicine and the director of the Les Turner ALS Center. Erin Spain: Let’s talk a little bit about ALS. Can you describe a person with ALS and how do you diagnose them? Robert Kalb: ALS or amyotrophic lateral sclerosis is a degenerative disorder, neuromuscular disorder where patients become progressively weak, and it’s due to the selective loss of motor neurons and the neurons that instruct the motor neurons what to do. Erin Spain: When somebody comes to Northwestern and they come to the ALS, the Les Turner ALS Center, what happens next? The constellation of issues that a patient will describe, you know, I don’t feel right or this isn’t right, I can’t do x, y, and z. It’s a combination of those symptoms and signs, these sort of things that a neurologist when examining a patient will say, oh, well this isn’t right, or there are there are no sensory symptoms and so the diagnosis of ALS is made by excluding other causes and assembling all the facts together in one unit. Many, many physicians who are quite experienced in diagnosis, diagnosing and managing ALS. You know, once a person gets to our clinic and we assemble all of the pieces of information and include the positive and the negative results, we’re pretty confident that, that a person will, you know, if a person has ALS that we can give them that diagnosis. Robert Kalb: Let’s just start by saying that most of most individuals who have ALS sporadic form of disease, which means that there’s no clear genetic cause and about 10 or 15 percent, there’s a clear single gene which is mutated that causes the disease and you can track it through a family, so all of our models of disease, so you need to, if you’re going to study the disease in a mouse or a rat or in tissue culture or any of a variety of other tools, genetically manipulate organisms, you have to create that model by manipulating the gene which was defective in the patients with familial disease.