The Research Plan

The Initiative

Answer ALS is the single largest coordinated and collaborative effort to end ALS in the history of the disease.

The project is creating the largest and most comprehensive foundation of ALS data ever amassed, encompassing clinical, chemical, genetic, protein, historical and biological data from an enormous sampling of ALS patients in the United States. In collaboration with machine learning and big data technology, the data will be mined to uncover ALS causes, subtypes, pathways gone awry and drug targets. This will establish a large and critical foundation for new clinical trials, develop new ways to categorize patients to identify specific druggable pathways and subtype biomarkers and disease pathophysiology to aid not only in early diagnosis of the disease, but also to monitor the efficacy of newly developed treatments.

This research project also could potentially provide deeper understanding of Alzheimer's, Parkinson's and other neurodegenerative diseases.

Jay Fishman

"After being diagnosed with ALS, I looked for the most aggressive project with the greatest possibility of yielding results through rapid benchmarks and milestones. This was that project."

Jay Fishman Chairman and Former CEO of Travelers and person living with ALS

Answer ALS originated as a result of the 2013 ALS Team Gleason Summit, which brought together leading researchers, patients, caregivers and advocates. The event was spearheaded by former NFL player Steve Gleason who lives with ALS and founded the ALS advocacy group, Team Gleason. The goal of the Summit was to create a plan to find a treatment or cure for ALS as quickly as possible.

A funding effort led by the Leandro P. Rizzuto Foundation and the Robert Packard Center for ALS Research has resulted in $20 million raised for Answer ALS thus far. The initial stakeholder funders are the National Football League, the PGA TOUR, ALS Finding a Cure (a project of the Leandro P. Rizzuto Foundation), Travelers, The Fishman Family and The Bari Lipp Foundation.

Our Ultimate Impact

We are harnessing the power of focused scientific research and data to find a treatment or cure for ALS in the next five to ten years.

The Answer ALS Plan

Since the first ALS gene was discovered 25 years ago, much has been learned about the disease. The last several years have seen exciting progress in ALS research, with new genetic causes explored and the initial utilization of induced pluripotent stem cells (iPS cells) derived from ALS patients in treatments.

Yet in spite of these discoveries and tools, the lack of new therapies or even good biomarkers yielded from these approaches has proven that single labs working in silos and simple animal models are not going to illuminate the disease's root cause, identify subtypes of the disease or define the best drug targets. Only a large-scale concerted and coordinated collaborative team effort will be able to make a difference, and make one quickly.

The Answer ALS research project is the largest coordinated scientific research project ever proposed for ALS. The initiative has brought together the world's experts in many different areas of influence in the study of ALS. (This includes leaders in iPS cell study, cell biology, drug screening, genomics, proteomics, clinical observation, big data, machine learning and more.)

With this project, we aren?t asking for answers to single questions, like "What is the next ALS gene to target?" or "What new animal models should we build?" Rather, we are comprehensively evaluating a very large patient population of 1000 participants, generating iPS cells from each and every patient, creating thousands of new and different iPS brain cell lines representing each of those patients, and performing the most comprehensive biological analytics ever—including DNA, RNA, protein and metabolism analysis—to yield a personalized database of thousands of petabytes of new ALS-specific information.

This will be the largest and most comprehensive foundation of ALS data ever amassed, and reflects real patients. In collaboration with experts in machine learning and big data informatics, this wealth of biological data will be mined to uncover ALS causes, subtypes, pathways gone awry and drug targets. It will serve as the foundation for new clinical trials, suggest new ways to subgroup patients to better discover successful drugs and to find drug-responsive biomarkers or diagnostics. Most importantly, this data is and will be publicly available for anyone to access, interpret and mine for valuable insight.

BeakersThe Answer ALS Plan Details

We are generating iPS brain cells from a population of at least 1000 ALS patients from across the USA to comprehensively evaluate their genetic and metabolic profiles and performing comprehensive longitudinal clinical observations.

The large amount of data collected will serve as a foundation—the largest foundation of basic chemical, clinical, genetic and biological data ever collected in ALS history—upon which to shape fundamental information about patient subgroups and their disease pathways, and ultimately with which to identify new druggable pathways, subgroup biomarkers and disease pathophysiology.

Phase 1 (Years 1 and 2)

We are operationalizing the program over two years. We have brought together six initial core clinical sites for patient participant identification and data collection. Those sites already exist, and the web-based clinical data collection portals are already in place, allowing for collection of identical clinical information across multiple sites.

We are generating the iPS cell lines through Cedars-Sinai Medical Center. They are generating iPS cell lines from supplied patient blood, which will then be differentiated to motor neurons and glia.

The cells are being uniformly grown in large quantities for shipment to the various labs. Studies are being carried out for transcriptomics (University of California, Irvine), epigenome (Massachusetts Institute of Technology), whole genome (New York Genome Center) and proteome (Cedars-Sinai Medical Center).

All data is being harmonized (Gladstone Institute) and analyzed centrally for patterns of clinical 'omic pathways, patterns of subgroups and patterns of disease pathways. This will be handled by Google X as well as other leading data collaborators. All data is and will be freely available to others via web access.

Phase 2 (Years 3+)

Once the data sets are analyzed, we anticipate that we will be able to evaluate ALS patients and identify at least two of the following:

ALS Subgroups: The extensive 'omics data acquired from Phase 1 will allow us to identify iPS cell lines, molecule analytics and specific ALS subgroups that patients would be grouped in for future clinical trials.

Drug Responsive Subgroups: The data gathered from the drug screening assays and/or the total 'omics data sets should allow the choice of existing or novel drug classes to be used in clinical trials and thus design future trials based on these patient subgroups. These studies may involve large or small subgroups of patients depending on the strength of the analyses. The 'omics analysis should help predict the best biomarkers to be employed in such studies, to help define drug activity (pharmacodynamic markers) and possibly drug efficacy.

Disease Biomarkers: The extensive 'omics should allow for identification of disease markers that are potentially useful for diagnostics and disease progression.

Disease Pathways and New Druggable Targets: The analysis will set the stage for follow-up research to explore and develop new drugs and/or employ existing drugs that have activity in the newly identified ALS disease causing pathways.

Our Research Effort

We've mapped out the steps of our research plan into a graphic that outlines each stage, from patient participation to data collection to the involvement of the research community. View Larger

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Leadership + Program Partners

Answer ALS is a multi-organizational group representing the committed work and innovative thinking of some of the brightest minds around the globe, including scientists, academics, organizations and individuals whose lives are personally affected by ALS.

Peter Foss

"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. 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.?

Peter Foss President of the ALS Finding a Cure Foundation, and General Manager of the GE/NFL TBI research project
Leadership Members

Program Governance

Executive Director 

Jeffrey Rothstein, MD, PhD (Johns Hopkins University)

Co-Directors

Clive Svendsen, PhD (Cedars-Sinai Medical Center)

Merit Cudkowicz, MD, MSc (Massachusetts General Hospital)

Clinical Program

Principle Investigators

James Berry, MD (Massachusetts General Hospital)

Nicholas Maragakis, MD (Johns Hopkins University)

Study Investigators

Stephen Kolb, MD, PhD (Ohio State University)

Jonathan Glass, MD (Emory University)

Timothy Miller, MD, PhD (Washington University)

Robert Baloh, MD, PhD (Cedars-Sinai Medical Center)

iPSC Generation

Principle Investigator

Clive Svendson, PhD (Cedars-Sinai Medical Center)

Study Investigator

Dhruv Sareen, PhD (Cedars-Sinai Medical Center)

Multi-Omics Analysis

Principle Investigator

Leslie Thompson, PhD (University California, Urine)

Study Investigators

Ernest Fraenkel, PhD (Massachusetts Institute of Technology)

Steven Finkbeiner, MD, PhD (Gladstone Institute, University of California, San Francisco)

Jennifer Van Eyk, PhD (Cedars-Sinai Medical Center)

Data Analytics

Principle Investigators

Ernest Fraenkel, PhD (Massachusetts Institute of Technology)

Steven Finkbeiner, MD, PhD (Gladstone Institute, University of California, San Francisco)

Program Managers

Emily Baxi, PhD (Overall)

Michelle Farr (Overall)

Sara Vaughan (Clinical Program)

Loren Ornelas (iPSC Program)

Brandon Shelley (iPSC Program)

Terri Thompson, PhD (Omics Program)

Program Partners

The Answer ALS research program partners are all the people and organizations who make this important research possible—and powerful. It's their combined experience, insight and influence that will allow us to make never-before-seen progress in the study and treatment of ALS.