ACT for ALS & ALS Strategic Priorities Community Update

November 06, 2023 | 11:00 - 1:00 PM

In February 2023, the National Institute of Neurological Disorders and Stroke (NINDS), the lead institute for Amyotrophic Lateral Sclerosis (ALS) research within the National Institutes of Health (NIH), completed a strategic planning process to identify the highest priorities for research that will lead to the discovery of effective interventions for the diagnosis, treatment, management, prevention, or cure of ALS. Extensive feedback from a large and diverse group of contributors resulted in a comprehensive list of priorities for the ALS community.  

NINDS and other organizations quickly moved into implementation efforts, creating programs to address many of the priorities outlined in the Strategic Priorities, such as a Public Private Partnership with the U.S. Food and Drug Administration and the Critical Path Institute. Additionally, many non-profit organizations have ongoing or new programs that address some of these ALS research priorities.  After 9 months of implementation, NINDS hosted an update for the ALS community on our efforts related to implementing the Strategic Priorities.

NINDS Director, Dr. Walter Koroshetz, provided a summary of the Institute's efforts as they relate to ACT for ALS and the implementation of the strategic priorities. Several non-profit organizations also presented their recent activities and progress that align with the strategic priorities.

Additional resources:


Frequently Asked Questions


Scientific Progress

Q: Are we getting closer to a cure for ALS? What stage is the development in?

A: ALS is a devastating disease, and there is a desperate, and urgent, need for improved therapies. Although several FDA-approved drugs slow the progression of ALS and may extend life by several months, there is currently no known cure for ALS. Better understanding of ALS is still needed to get effective treatments for both familial and sporadic forms of the disease. Gene-targeting treatments are in development for people with familial forms of ALS and there is optimism that these treatments may halt or even prevent the disease. Potential therapies are also being developed for treatment of sporadic forms of ALS.

Q: What is NIH doing to support drug repurposing research and commercialization as part of the strategic plan?

A: It is always faster to apply an approved drug to another indication.  Scientists who discover a potential therapeutic target usually look at approved drugs to see if any of them hit the newly identified target. Depending on how powerful and robust the effect is, a commercial partner might pursue an ALS indication. NINDS has a number of funding opportunities that are relevant to drug repurposing studies.  We encourage researchers who are interested in submitting a grant application for a drug repurposing study to contact NINDS program staff to discuss which of NINDS’s Translational and Clinical Research Funding Opportunities might be appropriate for them.  Contact information can be found at:

Q: What is NIH doing to identify/understand clinical heterogeneity in sporadic ALS? Specifically, what is NIH doing to characterize subtypes to enable more targeted treatment development?

A: This is an active area of investigation that several NIH-funded studies are addressing. For example, the Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium is studying the biological and clinical heterogeneity of ALS and related disorders such as primary lateral sclerosis, a more slowly progressing neurodegenerative disease that can convert into ALS. Furthermore, the recently funded ALL ALS clinical consortium expects to enroll a clinically heterogeneous cohort of people living with, or at high risk for, developing ALS and to collect biospecimens like blood or cerebrospinal fluid for further analysis from these individuals.  The goal of the consortium is to facilitate research aimed at obtaining mechanistic insights into what drives the heterogeneity and identifying therapeutic targets as well as biomarkers. Moreover, NIH-funded studies on familial forms of ALS, such as C9orf72-linked ALS, are identifying cellular defects that also occur in sporadic ALS and are opening new avenues for therapy development.

Q: What is NIH doing to advance patient-specific in vitro modeling as a tool to navigate heterogeneity, enable “subgroup-specific” target identification, identification of re-purposable drugs, and personalized treatment regimens? Is this a focus area?

A: The NINDS Human Cell and Data Repository (NHCDR) provides well characterized cell sources, including fibroblasts and/or induced pluripotent stem cells (iPSC) for ALS, and the iPSC Neurodegenerative Disease Initiative (iNDI) of the NIH Intramural Center for Alzheimer's and Related Dementias (CARD) is building a repository of genetically engineered cellular models of Alzheimer’s and related dementias, including FTD/ALS.  Researchers may request access to these in vitro models. Additionally, NIH is funding a number of research grants aimed at developing and utilizing cell-based models of ALS, including the sporadic form of the disease, to advance the development of subgroup-specific treatments. Information about NIH-funded grants, including their scientific abstracts, can be accessed on the NIH RePORT Categorical Spending webpage: (scroll down to “ALS” and click on the hyperlinked dollar figures). Additionally, you can conduct a more targeted search using the NIH RePORTER database:

Q: Has FDA, NINDS, or NIH determined a minimum size data set for ALS drug discovery and increasing our understanding of disease biology?

A: The minimum size data set depends on the scientific question asked and the ALS subtype(s) under consideration.


Funding for ALS Research

Q: How do we bring ARPA-H and their funding into the ALS landscape?

A: ARPA-H hires scientists to join as ARPA-H staff with their ideas for research. For example, an ALS scientist applying to work at ARPA-H may be an effective way to get ARPA-H into ALS.  ARPA-H also has a call for projects that would be open to ALS if it fits their remit. More about ARPA-H can be found at

Q: How can funding for ALS be increased?

A: In general, the NIH does not allocate a set amount of money for specific diseases or studies. Instead, the NIH system is open for any scientist to submit their best ideas for research studies on diseases, such as ALS, or other areas of biomedical research. Proposed research projects undergo a rigorous peer review process at the NIH and are then considered for funding.  The Advisory Councils of each NIH Institute must then recommend the project for funding before any funds can be awarded.  This review system, which is required by U.S. law, enables the NIH to make the best use of the funds appropriated to us by Congress.  Program staff is available to provide prospective applicants guidance on the process. You can find contact information for program directors at:

In addition to our general appropriations that are for all neurological diseases and related research, sometimes Congress appropriates funds for specific programs.  This is how NIH received $25 million in fiscal year (FY) 2022 and $75 million in FY 2023 specifically for implementing ACT for ALS.  These additional appropriations were the result of advocacy by people with lived experience of ALS, nonprofit organizations, and other ALS advocates.

Q: What is NIH doing to make sure PIs and trainees are being fiscally supported in their ALS research efforts and will there be an adjusted pay line for ALS-related projects like there are for Alzheimer’s Disease and related dementias?

A: Congress appropriates approximately $3 billion for dementia research each year. Because frontotemporal dementia (FTD) is considered an Alzheimer’s-related dementia, ALS research grants that are focused on the ALS-FTD disease spectrum qualify for this funding and have the same adjusted payline as other Alzheimer’s-related dementia grants. This covers most molecular studies at play in both disorders.  For example, studies of TDP-43, a protein that behaves abnormally in most forms of ALS as well as FTD, are eligible for the higher Alzheimer’s Disease and related dementias pay line. Potential grant applicants should talk to their Program Director about which studies are eligible for this funding.

Q: How much of the $100 million per year authorized in ACT for ALS has been approved for the research portion?

A: ACT for ALS was appropriated $75 million in FY 2023 funds. NIH spent approximately $33 million to support expanded access research grants (section 2 of ACT for ALS). These grant awards both provided access to investigational therapies and supported research. NIH spent approximately $42 million on the HHS Public Private Partnership (PPP) for Rare Neurodegenerative Diseases (Section 3 of ACT for ALS).


Expanded Access Research Grant Program

Q: What part of ACT for ALS indicates that the priority is the Expanded Access Program (EAP)?

A: Through the annual appropriations process, Congress directed NINDS to spend the funds that they appropriated for implementing ACT for ALS on expanded access first, then the public-private partnership.

Q: With the expansion of EAPs, trials and the current evolution of electronic clinical outcome assessments already underway, will the work of groups working on digital biomarkers be integrated via some digital health technology (DHT) or otherwise named work stream?

A: Once AMP® ALS has been launched, the AMP® ALS Steering Committee will work closely with CP-RND and follow FDA guidance to advance patient-focused clinical outcome assessments including DHT. ALL ALS and other clinical cohort studies in the ALS field provide critical infrastructure to advance DHT development. 

Q: How many patients will be treated across all four EAP funded studies (Trehalose, Pridopidine, RAPA501 and CNM-Au8), what is the total dollars committed, and where can I find more information about these studies across all 4 studies?

A: Trehalose: The grant awardees requested 3 years total funding for a study of Trehalose with 70 participants.  The total funding request for all 3 years of the study was approximately $18 million. NIH awarded all $18 million in FY 2022 (this is called a multi-year grant award*). 

Pridopidine: The grant awardees requested 4 years total funding for a study of pridopidine with 200 participants.  The total funding request for all 4 years of the study was approximately $34 million. NIH awarded $10 million in FY 2023, and grant awardees have requested approximately $24 million for FY 2024-2026**. 

RAPA-501: The grant awardees requested 3 years total funding for a study of RAPA-501 with 40 participants.  The total funding request for all 3 years of the study was approximately $29 million. NIH awarded $11 million in FY 2023, and grant awardees have requested approximately $18 million for FY 2024-2025**. 

CNM-Au8: The grant awardees requested 4 years total funding for a study of CNM-Au8 with 100 participants.  The total funding request for all 4 years of the study was approximately $45 million. NIH awarded $11 million in FY 2023, and grant awardees have requested approximately $34 million for FY 2024-2026**. 

* A multi-year funded award is funded in full at the start of the project period from a single fiscal year appropriation.  Thus, funding for future years of the study does not depend upon future appropriations from Congress.  Awardees must still meet predetermined milestones, such as enrollment targets, that have been negotiated between the awardee and NIH.

**In FY 2023, Congress directed NIH to single year fund grant awards in the expanded access research program.  In a single year funded grant, future year funding depends upon future appropriations from Congress.  Additionally, the awardee must meet predetermined milestones, such as enrollment targets, that have been negotiated between the awardee and NIH.

Grant award information can be found on NIH RePORTER ( To get a comprehensive list of grants funded in FY2022 and FY2023, use the “Advanced Projects Search” tool and select “all years” in the “Fiscal Year” field, and then scroll down to the “Opportunity Number” field and type in “RFA-NS-22-071; RFA-NS-23-012”.  We have done that search for you, and the results can be found at the following link.  However, this link will eventually expire, so you may need to do the search again:

Q: Is anyone building reusable infrastructure and tools so that subsequent EAPs will be less expensive and more efficient for data gathering in the future?

A: The HEALEY ALS Platform Trial and now the ALL ALS consortium should increase the impact of clinical research, including EAPs and make data gathering more efficient. Lessons learned from EAPs harmonizing data and gathering data into a centralized data portal could increase efficiency for future clinical research.

Public Private Partnership, including data sharing and natural history studies

Q: How are AMP-ALS and CP-RND getting guidance and input from people with lived experience in ALS?

A: AMP ALS has, from the outset, involved People with Lived Experience (PWLE) of ALS* as full participants and subject matter experts in its committees and working groups and will continue to do so throughout implementation. Co-development with PWLE has been impactful in the design of AMP-ALS and PWLE are seen by PPP participants as critical partners and subject matter experts.  CP-RND has followed a similar engagement approach and will continue those efforts.

*PWLE include those diagnosed with ALS, gene carriers, loved ones, caregivers and those who have lost loved ones to ALS.

Q: How does the ALL ALS Consortium plan to engage people who aren’t regularly seen at major ALS research centers, including people living in rural areas and underrepresented minorities?

A: The ability to engage a broad population of people living with ALS is an incredibly important issue that was one of many factors carefully considered in bringing together clinical sites for ALL ALS.  Nearly all sites are located where racial and ethnic minorities are highly represented, and we will be monitoring diversity as one of the milestones for this project. To facilitate inclusion of people living with ALS who are unable to travel (either locally or long distance) to large ALS care centers, the ALL ALS Consortium plans to do remote data collection as one way to allow such people to participate.

Q: How will enrollment be handled at clinical sites that participate in multiple studies (e.g., TargetALS, David Walk's natural history study, MOVR or ALL-ALS)?  Will it lead to longer times to recruit for each study because the participant pool (people who are able to travel to the site) will be divided among multiple studies?

A: NINDS recognizes that at some clinical sites, a potential study participant may be able choose between different studies when deciding to participate in research. However, notably, ALL ALS will recruit and enroll remote participants. ALL ALS may also allow participants who previously enrolled in person to be followed remotely. This remote enrollment could enable sites to include participants not typically eligible for participation in research studies. Thus, even though ALL-ALS includes clinical sites that also enroll for other studies, overall, NINDS anticipates remote enrollment in ALL ALS may allow a broader population of people with ALS the option to participate.

Q: How does the natural history consortium award funded by FDA correlate with the database and tissue collection work of ALL ALS and AMP® ALS?

A: ALL ALS will collaborate with other natural history studies in the field and discussions are underway to synergize efforts. NINDS intends to harmonize data collection to the extent possible and make all data available to the broad community through a centralized data portal.

Q: What is NIH doing to standardize data collection, including data from existing natural history studies?

A: NINDS is aware of existing natural history studies and is encouraging standardization of data collection to the extent possible to promote comparability across studies.

Q: How far are we from having one place where a person with ALS can enter their data and it is shared among the many existing natural history studies?

A: NINDS has pioneered use of GUIDS—global unique identifiers which allows identification of people who are participants in more than one research project. Many NIH- and disease-foundation-funded clinical studies and trials in ALS are already using GUIDS and although there are multiple GUID platforms, NIH intends to share data across studies to the extent possible.

Q: Is the knowledge portal open to data from clinical trials (for example, can the ProACT database be integrated into the knowledge portal) or is the knowledge portal only focused on observational natural history type studies?

A: During the AMP® ALS implementation phase, the AMP® ALS Steering Committee, in collaboration with a data working group that will be formed, will discuss which datasets will be most valuable to bring into the knowledge portal. We anticipate that data from the expanded access studies and multiomic studies in the ALS field will be made available through the knowledge portal.

Q: Will the inclusion/exclusion requirements of the clinical trials be changed to include PWLE that are further than 2 years from symptom onset?

A: FDA encourages the enrollment of broad disease populations in clinical trials to inform use of a therapy in patients with different characteristics and stages of the disease. However, the population enrolled in a specific clinical trial will depend on the drug development program and the anticipated effects of the drug-based mechanism of action.

For NIH-supported studies, inclusion/exclusion criteria are determined by the researchers conducting the clinical trials. NIH accepts applications for clinical trials at all stages of disease.  The target population is the one that best fits whatever the intended effect of the therapy.  For many efficacy clinical trials, researchers choose to only include people early in the disease because that is when they are most likely to see an effect of the therapy.  However, there are opportunities for people later in the disease to participate in research.  Studies funded through the NINDS expanded access research program only include participants who are not eligible for placebo-controlled trials.  These are often people who are more than 2 years from symptom onset.  Additionally, the ALL ALS Consortium will be recruiting people at all stages of disease with no exclusion based on length of illness for natural history and biomarkers studies.