Strategic Initiatives

The outpouring of support from the ALS Ice Bucket Challenge has allowed the ALS Association to champion numerous new strategic initiatives in order to build understanding of the disease, target new therapies, expedite clinical trials and make RNA and DNA sequencing data available for the entire ALS research community. These collaborative initiatives have already lead us closer to ALS treatments and a cure. Central to all new collaborations is the people living with ALS.

Neuro Collaborative

The Neuro Collaborative is a partnership between three leading laboratories in California. The synergetic model brings together complementary expertise to advance understanding of ALS and drug development. From sharing information to attracting industry investment, The Neuro Collaborative is an essential initiative that is driving potential therapeutics for ALS quickly toward FDA approval.

About the Neuro Collaborative

The Neuro Collaborative is a partnership between three leading laboratories in California – including Clive Svendsen, Ph.D. at Cedars-Sinai in Los Angeles; Steven Finkbeiner, M.D., Ph.D. at Gladstone Institutes, affiliated with University of California San Francisco; and Don Cleveland, Ph.D. at University of California San Diego. The synergetic model brings together complementary expertise to advance understanding of ALS and drug development. From sharing information to attracting industry investment, The Neuro Collaborative is an essential initiative that is driving potential therapeutics for ALS quickly toward FDA approval.

The ALS Association Commitment

In 2014, The ALS Association Golden West Chapter, along with Advisory Trustees Jim Barber and Linda Della, partnered with the National ALS Association to build the Neuro Collaborative concept. That year, following the amazing outpouring of support from the ALS Ice Bucket Challenge, The ALS Association committed $5 million dollars to the project. With additional help from The ALS Association Orange County and Wisconsin Chapters, the Neuro Collaborative has become an engine for ALS therapeutics.

Goals

The goal of the Neuro Collaborative is to establish and invest in a leading team of experts to efficiently advance ALS drug development together with industry partners. This complements other programs including the Drug Development Contract Program in the TREAT ALS™ portfolio investing in academic and industry partnerships. This synergetic model leverages open dialogue and the scientific expertise of leading researchers to achieve therapeutic milestones as quickly as possible. The collaboration is designed to reduce risk in the drug discovery process and attract pharmaceutical companies to invest in drug development and clinical trials for ALS. With success, potential therapies for ALS will move more quickly than ever toward FDA approval and the open market.

How the Neuro Collaborative advances the search for a treatment for ALS

Identifies small molecules designed to eliminate SOD1 and C9orf72 – the two most common genetic causes of ALS (i.e. antisense therapy).
Discovers novel, potential ALS drugs.
Moves drug discoveries into clinical trials through partnerships with pharmaceutical companies in order to leverage various expertise in drug development (chemistry, toxicology, regulatory), which is lacking in academia.
Reinforces the clinical trial process with pharmaceutical partnerships to move drugs toward FDA approval.
Provides tools to the broader community and industry partners such as available induced pluripotent stem cell (iPSC) lines and screening capabilities through the Brain Bot.
Each laboratory in the Neuro Collaborative focuses on different areas of ALS research to maximize shared knowledge and understanding of the complexities of the disease while increasing industry interest and investment in ALS drug development.

Key Players and Laboratories

The Neuro Collaborative partners with prestigious scientific advisors including: Dr. John Dunlop, Ph.D., Former Vice President of Neuroscience Innovative Medicines at AstraZeneca; Fred Gage, Ph.D., Professor in Laboratory Genetics at the Salk Institute; and Harry Orr, Ph.D., Professor of Laboratory Medicine and Pathology at University of Minnesota.

Laboratories that represent the Neuro Collaborative

The Cleveland lab at the University of California San Diego focuses on gene therapy and antisense therapy development.
They developed antisense therapy drugs against the C9orf72 gene. Dr. Cleveland’s lab is also developing gene therapy approaches against SOD1 and other targets that they identify. His lab is collaborating with Martin Marsala, M.D. at University of California San Diego and Brian Kaspar, Ph.D. at the Research Institute at Nationwide Children’s Hospital in Ohio to develop novel gene therapies for ALS.

Antisense technology, which The ALS Association has helped fund since 2004, has high potential to become a therapeutic treatment for ALS targeting both SOD1 and C9orf72 – the two leading genetic causes of familial ALS – to slow or even halt ALS progression. A major breakthrough in ALS, antisense technology reduces the production of SOD1 and C9orf72 proteins in the body.

The Svendsen lab at Cedars-Sinai in Los Angeles focuses on iPSC models to be shared globally.
They created clinical-grade iPSC lines from people living with ALS using a standardized, rapid and effective method through the Cedars-Sinai Stem Cell and Motor Neuron Core Facility headed by Dhruv Sareen, Ph.D. iPSCs are then converted to motor neurons, one type of cell that dies in ALS. iPSCs are like a person’s avatar in a dish, containing the same exact genetic information.

iPSCs are used to test drug efficacy and are paired with the clinical data of a person living with ALS. This helps scientists understand the connection between ALS symptoms and cell pathology. Advancements in iPSC development and technology are shared globally and can also help advance understanding of other neurodegenerative diseases.

The Finkbeiner lab at the Gladstone Institutes, which is affiliated with UCSF focuses on high performance drug screening and drug target validation.
They use robotic microscope technology, the Brain Bot, which tracks the health of cells (like motor neurons and glia) over many months from healthy to sick to death. It measures millions of individual cells, each tagged with their own signature, derived from people living with ALS and compares them to cells from healthy people.

The Brain Bot allows rapid drug screening and validation of potential ALS drugs by measuring whether a potential ALS drug improves or worsens the health of the cells.

Progress

Cleveland Lab:

Dr. Cleveland and Ionis Pharmaceuticals developed the first ever-antisense drug to treat a neurological disorder, ALS. The ALS Association initiated funding for the development of this revolutionary technology and has supported its development through continued funding for over a decade. A phase I/II study of the SOD1 antisense drug is currently underway since January 2016 with improved safety and chemical design that will test safety in persons living with ALS. A similar trial focused on antisense technology targeting C9orf72 is anticipated in early 2017 through partnerships with Ionis Pharmaceuticals and Biogen. The Cleveland team has also developed a C9orf72 mouse model that is shown to mirror some of the characteristics to people having the C9orf72 mutation and will be used for continued antisense drug development.

Svendsen Lab:

Dr. Svendsen’s lab has successfully made 24 iPSC lines derived from 11 healthy controls, 4 C9orf72 mutation carriers, 6 SOD1 mutation carriers and 3 sporadic ALS cases that are available to researchers worldwide. A recent review from Dr. Svendsen’s laboratory highlights the importance of iPSCs as a tool in ALS research that have the potential to identify new disease mechanisms and individual disease susceptibilities that cannot be revealed in other models. In efforts to improve iPSC models, Svendsen and colleagues also recently found that it might be beneficial to induce some aspects of aging in iPSC-derived motor neurons, thereby reflecting critical vulnerabilities similar to those of aged neurons that die from ALS.

Finkbeiner Lab:

Dr. Finkbeiner’s Brain Bot drug screening system attracts many industry partnerships. Using the Brain Bot, his team identified potential ALS compounds targeting autophagy, one mechanism the cell uses to get rid of unwanted by-products. His team found that adding potential autophagy compounds to motor neurons derived from people living with ALS was protective. Partnerships with several companies are in negotiations to optimize these compounds for a clinical trial. In addition, in January 2016 Gladstone Institutes, through the leadership of Dr. Finkbeiner, partnered with Biogen to discover novel drug targets for the treatment of ALS.

Project MinE

Project MinE is an international, large-scale research initiative devoted to discovering genetic causes of ALS and to ultimately find a cure. Project MinE is based on the fact that genes are thought to contribute, directly or indirectly, to many cases of ALS. Many ALS genes have been identified, but researchers suspect that many more, much rarer variants that affect the risk of ALS are awaiting discovery.

About Project MinE

Once Project MinE is concluded, new ALS genes, including rare genetic variants will be identified. Researchers can then zoom into these genes to better understand the disease pathways causing ALS and then ultimately understand whether those pathways can be targeted for new ALS therapies.

The ALS Association Commitment

The Association committed an initial $1 million in partnership with the Greater New York and Georgia Chapters, establishing the U.S. arm of Project MinE. Funding was announced in October 2014.

Goals

How Project MinE advances the search for a treatment for ALS

Collects samples from healthy people (7,500) and people living with ALS (15,000).
Sequences whole genomes to read the full sequence of DNA in each person.
Collects skin samples for researchers to make iPSCs.
Further analyzes the genome, such as how the genes are modified.
More research will place newly identified genes into ALS disease pathways that could potentially be targeted for ALS therapeutics.

Key Players

Entrepreneurs and people living with ALS, Bernard Muller and Robbert Jan Stuit, along with Leonard van den Berg, M.D., Ph.D., Director of Netherlands ALS Center, developed the Project MinE concept. In 2011, Bernard and met Robbert Jan Stuit and decided that together they could change the ALS field. After a tour of the Research ALS Center in the Netherlands, they found that 5,000 DNA samples collected from people living with ALS were stored in a freezer and were not being used because it was too expensive to conduct research experiments. That was the beginning of Project MinE.

Now 16 countries are participating in Project MinE – a global collaborative effort.

The ALS Association funding supports the U.S. arm of this initiative led by Jonathan Glass, M.D. at Emory University in Atlanta and John Landers, Ph.D., University of Massachusetts Medical School in Worcester, Mass.

Progress

It costs approximately $2,000 to sequence the whole genome of one person. As of August 1, 2016, Project MinE has achieved 35 percent of its total goal equaling 7,835 DNA profiles collected out of the total 22,500.

The U.S. arm of Project MinE has raised $1,500,395, which is 58 percent of its overall goal of $2,600,000. So far, 577 DNA profiles have been collected out of 1,000 goal.

Already from the data collected by Project MinE, researchers have discovered two new genes – NEK1 and C21orf2 – that were published in back-to-back articles in Nature Genetics. Two other genes, MOBP and SCFD1, were also identified as new associated risk genes that still require further validation. These gene discoveries will lead to the identification of novel ALS disease pathways that will be further explored as possible therapeutic targets.

Researchers funded by The Association are currently exploring how these newly identified genes contribute to ALS disease, by making mouse models that will be shared with the entire ALS community.

Genomic Translation for ALS Care (GTAC)

Genomic Translation for ALS Care (GTAC) is a collaboration with Biogen and Columbia University Medical Center (CUMC) to better understand how different genes contribute to various clinical forms of ALS. This will in turn help researchers design better, more focused clinical trials for the development of more effective treatments. This kind of precision medicine, in which treatment is tailored to each person’s unique genetic makeup, will be effectively applied to ALS.

The ALS Association Commitment

Goals

This initiative aims to set the stage for a nationwide effort to ensure the genomic characterization of all people with ALS. The study will follow 1,500 people living with ALS in the clinic over a three year period with three month visit intervals to collect clinical data, sequence their DNA and store blood samples to generate induced pluripotent stem cells (iPSCs). This information will allow the correlation of ALS clinical manifestations to the genetic causes and help stratify patients for future clinical trials. Ultimately, it will provide a basis for the development of precision medicine, or more individually tailored therapies for ALS.

How the GTAC advances the search for a treatment for ALS

Collects clinical progression data at the clinic
- Historical ALS data (onset and disease progression) for deep clinical phenotyping (comprehensive study of clinical history and disease progression)
- Family history
- Exposures and epidemiologic data
- Neurological examinations
Collects blood samples from people living with ALS
- To sequence whole genomes to read the full sequence of DNA of each participant
- Analyzes transcriptomics (study of messenger RNA (mRNA)
Collects pBMCs (peripheral blood mononuclear cells) archived to make iPSCs in the future
Shares information in a database that will allow for a large investigation of the clinical correlates of the genetic causes of ALS

Key Players

Matthew Harms, M.D., Director GTAC and Assistant Professor of Neurology at CUMC
David Goldstein, Ph.D., Director of the Institute for Genomic Medicine at CUMC and Professor of Genetics and Development at CUMC
Dhruv Sareen, Ph.D., Director of Induced Pluripotent Stem Cell Core Facility, Cedars-Sinai, Los Angeles.

Participant blood cells will be stored at the Induced Pluripotent Stem Cell (iPSC) Core, a facility supported by The ALS Association, at the Cedars-Sinai Board of Governors Regenerative Medicine Institute in Los Angeles led by Dhruv Sareen, Ph.D. Clinical data will be collected and curated through The ALS Association supported NeuroBANK™ at Massachusetts General Hospital in Boston. Each sample will have a unique identifier called a global unique identifier {GUID). Whole genome sequencing and transcriptomics are performed in collaboration with the New York Genome Center.

There are 10 centers across the U.S. and in Scotland collecting samples. Participating clinical centers include: Cedars-Sinai Board of Governors Regenerative Medicine Institute, Columbia University Medical Center, University of Michigan, Houston Methodist, Scotland ALS Clinic Network, University of Minnesota and Hennepin County Medical Center, University of Utah, University of Washington, Penn State Hershey Medical Center and Washington University in St. Louis.

Progress

Study started enrolling in June 2016 with a projected timeline of three years with follow-ups in three month intervals. Data will be shared immediately to the CGND consortium and publically at later stages. This collaborative effort is already responsible for identifying ALS gene TBK1 in 2015 that was published in the journal Science.

See the GTAC project page for more information and a recent progress report.

New York Genome Center - Center for Genomics of Neurodegenerative Diseases (NYGC CGND)

Recent discoveries have indicated that genes may contribute to a much larger percentage of ALS cases than previously thought. Finding these genes and understanding how they work will allow development of new therapeutic approaches.

About

The Center for Genomics of Neurodegenerative Disease (CGND) at the New York Genome Center (NYGC) is dedicated to the study of neurodegenerative diseases such as ALS and Alzheimer’s disease. CGND’s vision is to establish a framework for applying state-of-the-art genetics, genomics and bioinformatics to the study of neurodegenerative disease mechanisms by building partnerships with clinicians, basic scientists, geneticists and computational biologists.

The CGND has formed an international ALS Consortium to apply integrated genomics to advance the clinical diagnosis and care of ALS. Through a multidisciplinary collaborative effort that spans multiple ALS centers and bridges ALS clinicians and scientists, researchers are using whole genome sequencing to discover and study mutations and mechanisms underlying ALS.

The ALS Association Commitment

The CGND’s research program in ALS was established with the help of generous support from The Tow Foundation and The ALS Association that was announced in October 2014. The Association, in partnership with the Greater New York Chapter of The Association, committed $2.5 million to fund this research, directly from money raised through the ALS Ice Bucket Challenge. This matched a gift of $2.5 million from The Tow Foundation.

Goals

The CGND’s goals are to use whole genome sequencing to identify mutations that cause neurodegenerative disease. To gain insights into the relationship between mutations, gene expression and disease mechanisms, whole genome sequencing data will ultimately be integrated with other genomic-scale data such as RNA-Seq (i.e. RNA sequencing), RNA-protein interactions and DNA methylation patterns (i.e. a type of post-translational modification).

The CGND is helping to create a uniform system of collecting clinical annotation to better enable the integration of genomic data with clinical profiles. This information will be freely available to the research community in a data warehouse for whole genome sequencing and RNA-Seq analyses.

How the NYGC advances the search for a treatment for ALS

Target Groups: Familial ALS, Sporadic ALS, C9orf72 carriers
Data being collected now:
- Blood samples to make DNA
- Autopsy tissue to make RNA
- Some induced pluripotent stem cells (iPSCs)
- Clinical data (longitudinal clinical data targeted for ~1300 of a total of 1800 participants)
Pre-competitive Data Sharing with all Consortium Members, samples consented for broad sharing for all medical research
Current Studies:
- ALS gene discovery efforts: (1) understanding unexplained familial ALS and (2) increasing power through increased numbers of sporadic patients for co-analysis with existing datasets
- Genotype (i.e. genetic code)-phenotype (i.e. observable clinical characteristics) correlations
- Integrating whole genome sequencing (i.e. reading the full sequence of DNA for each participant) with tissue-specific transcriptomics (i.e. study of messenger RNA (mRNA)) for understanding the impact of regulatory variation and cell type-specific contributions
- C9orf72 promoter methylation

Key Players

- Hemali Phatnani, Ph.D., Director of the Center for Genomics of Neurodegenerative Disease, NYGC
- Tom Maniatis, Ph.D., Columbia University, Advisor
- Cheryl Moore, NYGC, Advisor
- David Goldstein, Ph.D, Columbia University, Advisor
- Robert Darnell, M.D., Ph.D., Founding Director, NYGC
The consortium is composed of research teams from Columbia University Medical Center, University of Pennsylvania, Massachusetts General Hospital, Hershey Medical Center at Pennsylvania State University, University of Maryland, Johns Hopkins University, Henry Ford Health System, University of California at San Francisco, Massachusetts Institute of Technology, Academic Medical Center, University of Amsterdam.

The NYGC CGND maintains partnerships with the Answer ALS Consortium, Genomic Translation for ALS Clinical Care (GTAC) Consortium and Target ALS (for the Post Mortem Core, iPS Core, biospecimen collection).

Progress

CReATe Consortium

The Clinical Research in ALS and related disorders for Therapeutic Develoment (CReATe) Consortium is a collaborative effort to foster the discovery and validation of biomarkers relevant to therapy development for people living with ALS and related disorders including frontotemporal dementia (FTD), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and progressive muscular atrophy (PMA).

About

CReATe is a Rare Diseases Clinical Research Consortium (RDCRC) that forms part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network.

In partnership with The ALS Association, CReATe is able to advance its goals through the release of an annual request for applications to fund biomarker pilot projects. CReATe also fosters biomarker development by making its substantial repository of biological samples available to the broader scientific community.

The ALS Association Commitment

The Association supports three areas through CReATe:

Pilot Biomarker Study: Dr. Benjamin Murdock at the University of Michigan in Ann Arbor, Mich. The project aims to identify immune cell populations to serve as biomarkers and therapeutic targets in ALS patients. The Association committed $50,000 over 1 year.
Sample Collection: Dr. Michael Benatar at the University of Miami in Miami. Supports a CReATe Consortium Biorepository to store biological samples collected from all study participants. Biomarker studies require that samples are collected, stored and processed in a harmonized manner, along with collection of clinical data. These samples are used to support biomarker studies within CReATe Consortium and within the broad scientific community. The Association committed $400,000 over 3 years. The CReATe Biorepository was announced in September 2015.
Sequencing Study: Drs. Paul Taylor and Jinghui Zhang at St. Jude Children’s Hospital in Memphis, Tenn. and Michael Benatar at University of Miami in Miami. The project aims to characterize clinical variability and progression amongst a large cohort of people living with ALS. The investigators plan on performing whole genome sequence analysis of at least 750 CReATe participants. All data will be made public to the ALS community. The Association committed $835,937 over 60 months.

Goals

How the NYGC advances the search for a treatment for ALS

Target Groups: Familial ALS, Sporadic ALS, C9orf72 carriers
Data being collected now:
- Blood samples to make DNA
- Autopsy tissue to make RNA
- Some induced pluripotent stem cells (iPSCs)
- Clinical data (longitudinal clinical data targeted for ~1300 of a total of 1800 participants)
Pre-competitive Data Sharing with all Consortium Members, samples consented for broad sharing for all medical research
Current Studies:
- ALS gene discovery efforts: (1) understanding unexplained familial ALS and (2) increasing power through increased numbers of sporadic patients for co-analysis with existing datasets
- Genotype (i.e. genetic code)-phenotype (i.e. observable clinical characteristics) correlations
- Integrating whole genome sequencing (i.e. reading the full sequence of DNA for each participant) with tissue-specific transcriptomics (i.e. study of messenger RNA (mRNA)) for understanding the impact of regulatory variation and cell type-specific contributions
- C9orf72 promoter methylation

Key Players

- Hemali Phatnani, Ph.D., Director of the Center for Genomics of Neurodegenerative Disease, NYGC
- Tom Maniatis, Ph.D., Columbia University, Advisor
- Cheryl Moore, NYGC, Advisor
- David Goldstein, Ph.D, Columbia University, Advisor
- Robert Darnell, M.D., Ph.D., Founding Director, NYGC
The consortium is composed of research teams from Columbia University Medical Center, University of Pennsylvania, Massachusetts General Hospital, Hershey Medical Center at Pennsylvania State University, University of Maryland, Johns Hopkins University, Henry Ford Health System, University of California at San Francisco, Massachusetts Institute of Technology, Academic Medical Center, University of Amsterdam.

The NYGC CGND maintains partnerships with the Answer ALS Consortium, Genomic Translation for ALS Clinical Care (GTAC) Consortium and Target ALS (for the Post Mortem Core, iPS Core, biospecimen collection).

Progress

NeuroLINCS

NeuroLINCS is a collaborative effort between numerous research groups that are experts in their field and have high proficiency in induced pluripotent stem cell (iPSC) technology, disease modeling, OMICs and computational biology.

About

Specifically, OMICs includes epigenomics (study of gene modifications that do not change the genetic sequence), transcriptomics (study of messenger RNA (mRNA)), proteomics (large-scale study of proteins) and cellomics (quantitative cell analysis). Their focus is to gain a deeper understanding of neuron and the causes of neurological diseases like ALS.

Not only is this study exploring ALS, but also Spinal Muscular Atrophy (SMA). Both are neurodegenerative diseases that effect motor neuron health resulting in muscle weakness and paralysis. There is no cure for either disease.

The ALS Association Commitment

The ALS Association committed $2.5 million with funding from the Greater Philadelphia Chapter over a five year period. Funding was announced in July 2016. This is a partnership with the National Institute of Neurological Disorders and Stroke (NINDS) to extend the current activities of NeuroLINCS, which is one of six National Institutes of Health (NIH) Library of Integrated Network-based Cellular Signature (LINCS) centers.

Goals

NeuroLINCS will investigate cell signatures from iPSCs generated from people living with both ALS and SMA. Currently, the study is analyzing the following 20 iPSC lines: four healthy participants, four people living with SMA, four people living with sporadic ALS, four people living with SOD1 ALS and four people living with C9orf72 ALS, which are the two most common genetic forms of ALS.

Using state-of-the-art methods, the NeuroLINCS program will create a wealth of cellular data that is patient specific. At the end of the study, analysis of the collected datasets will lead to identification of a network of unique cell signatures specific to both ALS and SMA.

The ultimate goal is to understand the commonalities and differences among the various types of ALS and SMA. This will lead to more efficient clinical trials to test treatments in specific patient groups that are more likely to succeed, getting researchers closer to effective treatments and cures. The results from this study will not only apply to ALS but also to SMA, thereby broadening its impact on the neurodegenerative field.

NeuroLINCS and the integrated team contributes significantly to Answer ALS, providing the building blocks and expertise required for the larger study planned for Answer ALS.

How NeuroLINCS advances the search for a treatment for ALS

Develops cell signatures of an array of human brain cell types under both a normal state and in response to chemical perturbations for comparison. A cell signature is a collection of data obtained from a set of tests that involve whole genomic sequencing (reading the DNA of a person’s entire genetic code) and OMICs studies as explained above.
Cell signatures are generated from iPSCs of people living with both ALS and SMA.
Collaboration is highly emphasized in this program. All data generated will be publically available worldwide.

Key Players

The research laboratories involved include:

Steve Finkbeiner, Ph.D., at Gladstone Institutes in San Francisco
Ernest Fraenkel, Ph.D. at Massachusetts Institute of Technology in Cambridge, Mass.
Jeffrey Rothstein, M.D., Ph.D. at Johns Hopkins University in Baltimore
Leslie Thompson, Ph.D. at University of California Irvine in Irvine, Calif.
Dhruv Sareen, Ph.D., Clive Svendsen, Ph.D. and Jennifer Van Eyk, Ph.D. all at Cedars-Sinai in Los Angeles

Progress

ALS Accelerated Therapeutics (ALS ACT)

ALS ACT is a novel academic-foundation-industry partnership with ALS Finding a Cure®, initiated with researchers from General Electric (GE) Healthcare and four academic Northeast ALS Consortium (NEALS) sites to accelerate treatments for people living with ALS. Through a multi-pronged approach, each partner will contribute to expediting clinical trials in ALS.

About

Goals

How the ALS ACT advances the search for a treatment for ALS

Supports development of neuroimaging tools as potential ALS biomarkers, a key unmet need in trials.
Supports projects focused on decreasing the production of misfolded proteins and reversing neuroinflammation, two major contributors to the disease process
Supports NeuroBANK™, a central repository for clinical research data in ALS that will host, curate and disseminate proteomic, genomic and clinical data. NeuroBANK™ serves the New York Genome Center (NYGC), Genomic Translation for ALS Care (GTAC) and Answer ALS strategic initiatives, along with many other projects.
Supports the NEALS Biorepository, which stores collected study participant samples (blood, cerebral spinal fluid, extracted DNA, urine, etc.) available to ALS researchers.
Supports phase IIA pilot clinical trials with relevant biomarkers aimed at developing novel ALS treatments.
Supports a gene therapy study by Robert Brown, M.D., Ph.D. that uses viruses to deliver gene therapy agents targeted at mutated ALS genes.
Supports a TDP43 PET Tracer Grand Challenge to generate a TDP43 biomarker to track TDP43 aggregation, in partnership with ALS Finding a Cure®.

Key Players

ALS Finding a Cure® was founded in 2014 by noted philanthropist and Founder and Chairman of Conair, Leandro (Lee) Rizzuto, as a tribute to Christie Rizzuto, Lee’s daughter-in-law who was diagnosed with ALS in 2009 at the age of 41. Under the joint leadership of Lee Rizzuto and Peter N. Foss, ALS Finding A Cure® is focused on identifying the gaps in the scientific understanding of ALS that are preventing the development of a cure.

Top ALS investigators contribute to ALS ACT, including:

Merit Cudkowicz, M.D., MSc, Massachusetts General Hospital in Boston
Robert J. Brown, Jr. M.D., D.Phil., University of Massachusetts in Worcester, Mass
Stanley H. Appel, M.D., Houston Methodist Hospital System in Houston
Nazem Atassi, Ph.D., University of Massachusetts in Worcester, Mass
Clive Svendsen, Ph.D., Cedars-Sinai in Los Angeles
Nadeem Ishaque, Ph.D., and Thomas Gentile, M.B.A., GE Healthcare

Answer ALS

Answer ALS is an initiative spearheaded by Steve Gleason to challenge ALS researchers to come up with a solid plan to find a cure for ALS. Its strategy includes two impact goal arms that help people living with ALS live more productive lives and to ultimately bring top ALS researchers together to find a treatment or cure. Projects funded as part of other strategic initiatives, ALS ACT and the Neuro Collaborative, form an important foundation for Answer ALS.

About

Goals

Answer ALS has two impact goals:

Immediate impact: To find ways to help people living with ALS to live more productive lives. Initiatives include supporting affordable assistive information technologies and services to allow people with ALS to live the most productive life possible without financial burden.
Ultimate impact: Funding a coordinated, collaborative effort to bring together the world’s leading ALS researchers to work toward treatments or a cure in the next 5-10 years.

How The ALS Association supports ANSWER ALS

How ANSWER ALS advances the search for a treatment for ALS

Combines genomics (study of DNA), transcriptomics (study of messenger RNA (mRNA)), epigenomics (study of gene modifications that do not change the genetic sequence), proteomics (study of proteins), lipidomics (study of lipids or fat cells), generation of induced pluripotent stem cells (iPSCs) and deep clinical phenotyping (extensive overview of a patient’s clinical history and observable traits) to discover ALS disease subtypes and response to drugs.
Uses a personal monitoring device and a smartphone app to collect clinical data from participants 24/7.
Analyzes data on a large scale to ultimately identify new ALS druggable pathways and biomarkers and to design more efficient clinical trials.

Key Players

Jeffrey Rothstein, M.D., Ph.D., Johns Hopkins University, Baltimore
Clive Svendsen, Ph.D., Cedar-Sinai Medical Center, Los Angeles
Merit Cudkowicz, M.D., MSc., Massachusetts General Hospital, Boston

(left to right) Dr. Jeffrey Rothstein, Dr. Clive Svendsen and Dr. Merit Cudkowicz

Answer ALS clinic sites include: Massachusetts General Hospital, Cedar Sinai Medical Center, Johns Hopkins University, Ohio State University, Emory University and Washington University St. Louis.

Progress

ALS ONE – Massachusetts ALS Partnership (MAP)

Kevin Gosnell, founder of T&K Asphalt Services, Inc. and a person living with ALS, launched ALS ONE to bring together leading neurology experts and care specialists in Massachusetts in partnership to leverage their institutions’ strengths to expedite progress toward finding a treatment for ALS by 2020.

About

The ALS Association and the ALS Finding a Cure® are working together with ALS ONE to develop and fund appropriate clinical and research initiatives to maximize synergies that will make a significant impact on the disease. This collaboration was founded in January 2016 and solidified in November 2016. Each partner is contributing $2 million to this strategic initiative, for a total commitment of $6 million this year.

Goals

Kevin Gosnell brought together the top leaders, researchers, doctors and caretakers in ALS within Massachusetts, to join forces to bring the strengths of their prestigious institutions to an ambitious plan: to bring a treatment to persons with ALS by 2020.

By working together to fund and develop a treatment, they will demonstrate their shared commitment to fighting ALS while also continuing to provide high-level care for those who have already been diagnosed. By unifying resources, expertise and dedicated teams into a large coordinated team, individual goals will be aligned to move ideas and products quickly from inception to trial and from idea into care practice.

How ALS ONE advances the search for a treatment for ALS

Leverages the expertise from each research institution though sharing ideas and responsibilities to advance each of the strongest therapeutic opportunities identified forward.
Eliminates unnecessary duplication and expedites the path to find an ALS treatment.
Improves care for people living with ALS by creating more access to clinical trials through education and transportation, as well as providing technology, equipment and support services.

Key Players

Kevin Gosnell late founder and CEO of ALS ONE was diagnosed with ALS in spring 2015 and passed away August 8, 2016 from complications of the disease. He founded ALS ONE in January 2016 with a vision to bring the best minds in the ALS community to work together.

The ALS ONE leadership team is comprised of many of the top ALS experts in the world, including:

Nazem Atassi, M.D., James Berry, M.D. and Merit Cudkowicz, M.D., MSc. of Massachusetts General Hospital in Boston
- Building a regional ALS clinical trials network to rapidly and efficiently bring the most promising new therapeutic ideas to trials in people living with ALS
- Initiating a new clinical trials to test promising treatments which targets inflammation
- Building a translational pipeline that includes developing new lab tests and imaging tools for testing treatment efficiency
Ron Hoffman, Founder and Director CCALS
- In partnership with Drs. Atassi, Berry and Cudkowicz, CCALS is improving patient access to multidisciplinary ALS care and research studies using novel technology and nursing resources.
Steven Perrin, Ph.D., ALS Therapy Development Institute (ALS TDI) in Cambridge, Mass.
- Developing a CD40 ligand as a therapeutic approach for ALS based on preliminary data generated at ALS TDI in collaboration with academic and industry partners
- Integrating preclinical testing (mechanistic, pharmacodynamics and pharmacokinetic data) of promising therapeutics with the regional clinical trials network
Robert Brown Jr., M.D., Ph.D., University of Massachusetts Medical School in Worcester, Mass.
- Developing strategies to silence the production of toxic RNA and proteins produced from the expanded C9orf72 gene in mouse models, with the intent to move studies into clinical trials
- Augmenting the clinical infrastructure to enhance integration with the regional trials network

Lucie Bruin, Ph.D., M.B.A., Chief Scientist of The ALS Association and Stephen Winthrop, a member of The Association’s National Board of Trustees, both serve on ALS ONE’s Board of Directors.

Partners in the initiative include The ALS Association, ALS Finding a Cure®, ALS Therapy Development Institute, Massachusetts General Hospital, University of Massachusetts Medical School and Compassionate Care ALS (CCALS) and ALS ONE.

Strategic Initiatives

Neuro Collaborative

Project MinE

Genomic Translation for ALS Care (GTAC)

New York Genome Center - Center for Genomics of Neurodegenerative Diseases (NYGC CGND)

CReATe Consortium

NeuroLINCS

ALS Accelerated Therapeutics (ALS ACT)

Answer ALS

ALS ONE – Massachusetts ALS Partnership (MAP)

See the ALS Ice Bucket Challenge Progress!