FAQs

Answer ALS is the first initiative of its kind, so there are a lot of questions that potential participants have about the scope of the initiative, the specifics of participation and more. We've tried to address some of the more common questions here to better illustrate our approach, plans and goals. 

I read where Answer ALS is the largest coordinated ALS research effort. Why is important to be large?

The Answer ALS research project is the largest coordinated scientific research project ever undertaken for ALS. Answer ALS will comprehensively evaluate a very large population (1000 participants with ALS), generate induced pluripotent stem cells (iPSCs) from each and every participant, create thousands of new and different iPSC brain cell lines—representing each of those participants, and perform the most comprehensive biological analytics ever to create a personalized database of thousands of petabytes of information. This will be the largest and most comprehensive foundation of ALS data ever amassed—and will reflect real people living with ALS. The initiative brings together the world's experts in many different areas of influence in the study of ALS. (This includes leaders in iPSC cell study, cell biology, drug screening, genomics, proteomics, clinical observation, big data, machine learning and more.)  Answer ALS is designed to be the most detailed combined clinical, molecular and biochemical assessment of all ALS research. 

Our meaning of "large" is not only based on numbers and volume—but also on extending our reach into new and innovative areas where ALS research has not travelled before. So while participant numbers, pioneering biomedical research and petabytes of new data are our primary focus—our program is also tremendously enhanced in size and capability through our alignments with Google, Microsoft, the New York Genome Institute and others. Additionally, and perhaps one of the most important aspects of Answer ALS, is our commitment to develop information that is available to researchers across the globe, at NO COST, to advance their research as well. So, while our initiative is large in scale and scope, we are openly offering all we develop to the ALS research community so we may all work towards a solution as rapidly and efficiently as possible.

Answer ALS is based on utilizing iPS cells for research. What exactly is an iPS cell?

The Answer ALS research teams derive induced pluripotent stem cells (also known as iPS cells or iPSCs) from participant blood donations to the Answer ALS study.  IPSCs are a type of pluripotent stem cell (meaning a type of stem cell that can become any of the cell types that make up the body) that are generated directly from adult blood cells (not embryonic cells). We use the IPSCs to make motor neurons which may then aid in the discovery of factors that either cause or influence the course of disease in ALS.

The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells. Pluripotent stem cells are an excellent tool to help study ALS because they can propagate indefinitely (therefore providing researchers with plenty of material to study) and are derived from individual patients. Patients with ALS may experience highly variable disease courses. The opportunity to study cells that are representative of each individual patient participant with ALS means we may learn more about the factors that contribute to their particular form of the disease—and  consequently generate their ALS signature.

Other groups are also working with iPS cells. How is Answer ALS' research different?

Participant Coding at a National Level: Answer ALS is leveraging the National Institute for Health's "Global Unique Identifier" (GUID) coding system. De-identified participant data will be coded using GUID which is composed of a sequence of random numbers and letters [example: 7DE9KOS9S] and is unique to each participant. Use of the GUID keeps participant information separate from that of other participants without using names, addresses, or other private identifying information. The unique code also allows all submitted information on a single participant to be linked together giving researchers access to information that may have been collected elsewhere. Using GUID allows our participants to participate in other clinical trials with the same GUID assigned here. This prevents unnecessary redundancy and ease of de-duplication in understanding outcomes.  This is also a key request from the ALS community.

Participant "Wearables" Technology: Many of our participants will be given a Microsoft Band for the study. The Microsoft Band is a very easy to wear and comfortable wristband that will allow for a number of bio-measures, more than just movement, to be acquired from our participants. These bands have been customized for the Answer ALS study and when paired with a smartphone (either Android or iOS platform), may reveal previously unappreciated details about disease onset and progression. To this end, we have designed games to specifically assess motor function in ALS. The band will also be used to monitor many other patient parameters including breathing, speech, heart rate, sleep and general movement. The information will be automatically collected and assessed in a secure cloud environment that requires very few active measures from participants. This will allow their continued participation even as physical capabilities decline.

Biosample Collection: Answer ALS will use blood samples from participants to complete whole genome sequencing (to identify potentially disease causing/modifying genes) and to isolate cells which will be then be used to generate IPSCs. In the later process, cells known as peripheral blood mononuclear cells (PBMCs) are first transformed into IPSCs and subsequently into motor neurons—the exact cell type that degenerates in ALS. The use of blood vs. skin has many benefits, not the least of which is participant comfort and extending the role of participation without the need for multiple skin biopsies. For example, a single blood donation from a patient will provide sufficient material to facilitate multiple studies across institutions to study the DNA, RNA and proteins of these cells in a variety of ways. To do the same number of studies from a skin biopsy would require skin from almost the entire forearm of a patient!  

Bioinformatics, Analytics and Multi-omics: No other ALS study is delving as deeply into the cell biology of IPSC-derived motor neurons as Answer ALS. We are leveraging the latest research techniques to accomplish complete cell imaging, transcriptomics, metabolomics, proteomics and epigenomics. We will provide more details on what kind of information this will tell our researchers—but essentially this detailed genetic and metabolic information will allow us to understand each participant's "ALS Signature" and then identify subtypes based on those signatures. This is a new level of fidelity never before accomplished in ALS research.

Biosample Banking and Sharing: Answer ALS is "banking" all of the patient samples (including blood plasma and serum and cerebrospinal fluid (CSF)) at the NEALS (Northeast ALS Consortium) biorepository at Massachusetts General Hospital. IPSC lines will also be banked at Cedars-Sinai. Banking will allow other researchers from across the global research community to access these precious samples. This was a key request from the ALS patient community—sharing their biosamples so that they don't have to "keep donating", rather their precious donations of blood, CSF, etc will be put to optimal use across the research community.

Knowledge Sharing and Collaboration: In addition to the availability of biosamples, we are also making all of our resultant data accessible to the global research community via the Answer ALS Knowledge Network. We believe in the power of true collaboration and will share all data in a secure collaborative environment with our peers, not only in the ALS Community, but with all researchers looking for insight into ALS and neurodegenerative diseases. 

Funding: We are funding this amazing research through private philanthropy. The science is being driven through an intensive collaboration with the best scientists and Universities around the nation. We are not driven by corporate/biotech interests and we are not asking the patients to fund this with their already constrained resources. Our goal is to create the greatest benefit for our families at the least cost to them. 

Is Answer ALS working with other groups who are doing similar research?

Yes. We need our partners and pride ourselves on expanding collaborative efforts. Answer ALS is a cooperative venture that involves leading researchers and investigators who have a long history of successful, productive collaboration. Many of our researchers bring expertise not only from the ALS field, but from other areas of neurodegenerative disease research. This is vitally important because we now know that a number of disease pathways may be common to multiple neurodegenerative diseases including Alzheimer's, Huntington's, Parkinson's and multiple sclerosis. Answer ALS has recruited key scientists in the field of  IPSC research.  Scientists  who continue to pioneer the development and optimization of this technology, with proof points of claims demonstrated and made publicly available through peer-reviewed publication and scientific communication. The Answer ALS project network is diverse and includes cross fertilization with other significant ALS research initiatives, including  the government (NIH, NINDS) and private philanthropy (eg. TargetALS) to create new synergies and efficiencies.

Answer ALS has harnessed the research capabilities of leading ALS and neurodegenerative research labs around the world. These global researchers lead the way in full-spectrum IPSC technology from basic research, through translational research, to preclinical and clinical development. 

This unparalleled depth and breadth of expertise provides:

  • A comprehensive 'omics perspective brought through whole genome analysis, proteomics, metabolomics, epigenetics, as well as robotic phenotyping
  • Ability to bring to partnership big data expertise and active partners (eg Google)
  • Thanks to deep partnership and inclusion of NEALS, a distributed and already-established network of participant collection clinical sites creating more efficient collection of data and integration with clinical observation data (6 initial collection sites proposes across country, at major Clinical locations)

We will always be open and available to explore new partnerships, including those with our fellow researchers completing  similar/complimentary research whether in ALS community and beyond.

I have already given my tissue to another lab for a research program. Will I have to give tissue again? If so, why?

The answer to this is, mostly likely yes. We are using blood cells known as PBMCs to generate IPSCs and ultimately motor neuron. Unfortunately, if you've already donated a skin biopsy, this cannot be used by our researchers to generate a sufficient number of motor neurons to complete all the modes of analysis we require for this study.

If I am participating in multiple programs, will all my information be able to be shared with the different programs?

Not every ALS research program has made the commitment to openly share deidentified biosamples and data with the broader global research community as Answer ALS has done. There are still a number of laboratories and private programs that use the information for proprietary or "for profit" purposes.  That is NOT the ethos of Answer ALS. We are focused on releasing information as soon as we can—operating with the sense of urgency our participants and families expect.  All tools, data, and knowledge is peer-reviewed and will be made available to the global ALS community as the research proceeds—not just at the conclusion of the effort. 

Answer ALS includes partner organizations, like NEALS, to ensure our participants and partners are involved in the research process.  Answer ALS is explicitly set up to create a repository of knowledge and tools available to the global ALS research community, not only for Answer ALS investigators/labs.

Where does my sample go, once it has been taken?

The Answer ALS program stretches across multiple disciplines, starting with the clinic, moving to basic science and ending with big data. Experts from each field have been carefully chosen to lead the research at every point. The figure below (view larger) explains the program flow from a patient entering the clinic and donating biological samples, to the generation and integration of data from the clinic, wearable devices, whole genome sequencing and multi-omic assessment of iPSC-derived motor neurons. Ultimately Answer ALS will generate the largest and most comprehensive collection of ALS data ever amassed. This data will be made freely available to the ALS research community along with a complementary biorepository of patient biofluids to be housed at the NEALS sample repository at MGH.  

Fig01-InfographicALS06.jpg#asset:583

I watched the Answer ALS video. Can you explain what all the "omics" are and why they are important?

Our omics process begins with an in-depth analysis of your DNA (genomics). Your genome is your blueprint and determines everything from the color of your hair to your disease predisposition. Do you have genes already linked to ALS? Can we identify new associations between genes and ALS?

Next we will look at your epigenome. The epigenome helps to determine which genes are expressed within a cell. If you think of DNA as the roads on a map, then your epigenome would be the traffic lights and road signs—a set of instructions that tell your cell if and when to express various genes. While some aspects of your epigenome are inherited from your parents, others can be influenced by your lifestyle and environment. We want to understand if changes in how your DNA is regulated could be linked to the ALS disease process.

Finally, we will then focus to a set of omics that will tell us more about how your motor neurons are actually functioning. What genes are they expressing (transcriptomics)? What proteins are they making (proteomics)? And following intense cellular activity, what breakdown products (metabolites) does your motor neuron produce (metabolomics)? How does this vary from a healthy motor neuron and can that tell us something about the disease process? Integrating the results from all of these omics will provide an unprecedented level of analysis that could help us to identify new mechanisms of disease initiation and progression as well as revealing new targets for diagnosis, prophylaxis and treatment—in short, we hope to use these results to find an answer to your ALS. 


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What do you hope to accomplish with the "Big Data" and the "machine learning" from all the data?

Through Answer ALS and other community partner initiatives, as increasingly large amounts of genomic and other participant/family information becomes available, more efficient, sensitive, and specific analyses becomes critical.  Answer ALS and our community partners will ensure that our ability to collect, process, and securely store information does not outpace the ability of our researchers to analyze the data.  Answer ALS, working with our community partners, will leverage state-of-the-art big-data and machine learning technologies to analyze information in ways never before imagined. 

Answer ALS is working with our community partners, and in the larger research network, to design and execute an unprecedented system to effectively and efficiently combine/integrate our community data—leveraging existing capabilities to the extent practicable and connecting the wealth of information that already exists from basic molecular research, clinical insights, environmental data and others. This approach will allow us to integrate the data not only from Answer ALS but also with other research data, clinical information, participant input, participant health record information, family medical histories, environmental data, medical sensor data (wearables) and more.  

In collaboration with our ALS community partners, including experts in machine learning and big data informatics, this wealth of data will be "mined" and analyzed to uncover ALS causes, subtypes, pathways gone awry and drug targets.  It will serve as the foundation for new clinical trials, new ways to subgroup participant to better discover successful drugs, to find drug responsive biomarkers or diagnostics.

We are calling this data effort the ALS Knowledge Network. The Answer ALS Knowledge Network will enable researchers to share these new insights, techniques, processes and ideas. The connections and patterns that emerge will suggest testable hypotheses and new conceptual syntheses for researchers, implicate mechanisms of disease for researchers and clinicians, and enable more precise diagnoses and treatments for individual participants. Collectively we are fostering an innovative collaborative community focused on accelerating insight and discovery.

What does "sub grouping" or "sub-types" mean and what do you hope to accomplish by doing that?

ALS has been long thought to be a single disease. Current research indicates that ALS can more accurately be described as a "syndrome" of neurologic degeneration. ALS is a highly variable condition and this variability has prompted a number of questions surrounding the existence of ALS subtypes, which divide ALS participants into groups based on clinical or demographic features. 

Doctors have identified the major "types" of ALS: 

  • Sporadic ALS—The most common form of this syndrome. The individual experiences a progressive deterioration of the nerve cells and experience loss of motor function in hands, feet, arms, and legs, in addition to difficulty chewing, speaking, and swallowing
  • Familial—Used to classify participants who have one or more members of the family who has also been afflicted with this syndrome. This, however, is very rare and accounts for only about ten percent of ALS cases.

New research is signaling that perhaps previous "typing" of ALS has been overly simplistic and that in reality, ALS is comprised of many different sub-types of the disease, all with slightly different causes and courses of progression.   

Because of the chronic multifaceted and progressive nature of ALS, there are many possible ways to define subtypes. For example, ALS subtypes may be based on motor location onset (eg, 'bulbar palsy'), cognitive features (with or without dementia), rate of progression or a combination of these. There may also be subtypes based on genetically determined forms of ALS. 

Answer ALS will use advanced multi-omics data analysis as well as participant clinical data to identify "clusters" of research interest.  These clusters will be further analyzed for common linkages. If ALS subtypes result from independent causes and pathophysiological processes, then they can be thought of as separate disease processes. On the other hand, if there is a common cause then subtypes must result from participant specific activity that change the manifestations of the disease. Subtype findings could lead to more highly targeted research and, eventually, new treatments for ALS designed for an individual's "type" and "subtype" of ALS.

What do you mean by "disease biomarkers"?

Biomarkers are by definition an indicator of a particular condition in the body. Disease or "diagnostic" biomarkers are the signs and signals of a disease process occurring within the body.  To date, we do not have a disease biomarker for ALS. Rather ALS diagnosis continues to be a diagnosis of exclusion—meaning that all other conditions must be ruled out first.

Diagnostic biomarkers are any small molecules that can be detected in the blood or cerebrospinal fluid (CSF) that are associated with a disease. Knowing the biomarkers for ALS would enable earlier and more accurate diagnosis of ALS, with a greater chance for earlier treatment to potentially alter the disease course. Biomarkers would also make it possible to measure the effectiveness of different drug treatments in clinical trials. 

If I participate in this program, how often will I have to participate?

Ideally, participants will have 5 study visits;a  screening visit and a  3, 6, 9 and 12 month follow-up visit. There will be a one-year post-participation follow-up period, during which participants will receive an email or phone call interview once every 3 months. During the first year, samples will be collected, breathing, muscle strength, spasticity, general function and cognitive behavior will be assessed.

What do I have to do to be part of the Answer ALS research program?

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02574390

Contacts

Betsy Mosmiller, BA
410-502-0495
emosmil1@jhmi.edu

Aiana Rodriguez, BS
443-287-0627
arodri47@jhmi.edu

Locations

  • Cedars-Sinai Medical Center, Los Angeles, California, United States, 90048 
  • Emory University, Atlanta, Georgia 30322
  • Johns Hopkins University, Baltimore, MD 21205
  • Massachusetts General Hospital, Boston, Massachusetts, 02114
  • Washington University School of Medicine, St Louis, Missouri, 63110
  • Ohio State University Wexner Medical Center, Columbus, Ohio, 43221
If there is no Answer ALS clinic site close by, can I have my blood samples submitted remotely?

We continue to explore new ways to bring new participants into this study. Currently, however, the only places to participate are the listed clinic locations.  We will keep you posted when there are additional clinics or remote ways to participate.