Overview

ALS Finding a Cure^® (ALSFAC) invites proposals for research aimed at defining the biological mechanisms that determine why ALS develops in some individuals but not others. This initiative will support mechanistic studies that investigate determinants of motor neuron vulnerability, pathways that confer resistance to neurodegeneration, and biological events that initiate ALS prior to clinical symptom onset. Projects may include laboratory-based, computational, and human-focused research using model systems, biospecimens, datasets, or clinical populations.

Background and Rationale

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no cure and limited therapeutic options. Despite advances in genetics, molecular biology, and therapeutic development, the earliest biological events that determine disease onset remain poorly understood. Why do some individuals develop ALS while others—despite similar genetic or environmental exposures—do not? Understanding the biological mechanisms that sustain resilience—and those that drive vulnerability—represents a critical frontier in ALS research and may reveal new therapeutic targets and earlier intervention opportunities.

Scope of the RFP

ALSFAC invites proposals addressing motor neuron vulnerability, biological resilience, and early disease initiation.

Eligibility

Open to investigators at academic, clinical, and research institutions worldwide. Applicants at all career stages are eligible. Cross-institutional and multidisciplinary teams are encouraged.

Funding and Award Information

Number of Awards: Up to 3
Funding Amount: Up to $400,000 USD total per award
Grant Duration: Up to 2 years
Indirect Costs: Maximum of 15%
Milestone-driven progress will be expected.

Application Process and Timeline

This funding opportunity will use a two-stage application process consisting of a Letter of Intent (LOI) followed by invited full proposals.

Stage 1 — Letter of Intent (LOI)

LOI Requirements:

• 1–2 page concept description (Title, brief overview, expected outcomes)
• Investigative team and institutional affiliations
• Biosketches for key personnel

Stage 2 — Invited Full Proposal

Selected applicants will be invited to submit full proposals approximately five weeks after notification of results of LOI review.

Full Application Requirements:

• Cover letter
• Project Plan
• Background
• Timeline
• Investigator CVs
• Financial Disclosure Form

Anticipated Award Timeline

Timeline:

• Initial Letter of Interest (LOI) Submission Due: Monday, March 30, 2026
• Notification of LOI Submission: May 2026
• Full Proposal Deadline: June 2026 (5 weeks after invitation)
• Award Decisions: Summer 2026
• Project Start Date: October 1, 2026

Review Criteria

• Scientific innovation and originality
• Relevance to ALS susceptibility, resilience, and disease initiation
• Potential to advance understanding of ALS onset biology
• Translational potential • Strength and complementarity of investigative team
• Feasibility and rigor of approach
• Milestones and execution plan

ALSFAC is particularly interested in high-risk, high-reward ideas capable of shifting current paradigms.

Submitting an LOI

Please submit a completed LOI with contact information to: https://app.box.com/f/0f7d5b108a5d4921a4f789ae37378e8c

Contact

Questions may be directed to: info@alsfac.org

Overview:

ALS Finding a Cure^® is pleased to announce a Request for Proposals (RFP) to support innovative research projects leveraging Artificial Intelligence (AI) and Natural Language Processing (NLP) to advance ALS discovery. This funding opportunity seeks to catalyze transformative research that integrates AI-driven methodologies to improve diagnosis, biomarker identification, disease progression modeling, and therapeutic target discovery in ALS.

Background:

ALS is a devastating neurodegenerative disease with no cure and limited therapeutic options. AI and NLP offer the potential to revolutionize ALS research by enabling the extraction of meaningful insights from complex datasets, including electronic health records (EHRs), published medical literature, clinical trial data, omics datasets, and real-world patient-reported data. Through this RFP, we aim to support high-impact projects that will enhance our understanding of ALS and accelerate novel therapeutic strategies.

Examples of large data sources include but are not limited to:
Answer ALS, ALS Compute, UK Bio Bank. ProACT, NeuroBank, Project MINE

Scope of the RFP:

We invite applications proposing AI and/or NLP-based approaches to address critical challenges in ALS research. Areas of interest include, but are not limited to:

• Drug Discovery and Repurposing: Machine learning-based identification of potential ALS drug targets or repurposed therapies using AI-driven drug screening techniques.
• Biomarker Discovery and Validation: Integration of AI/NLP with multi-omics, imaging, and patient-reported outcomes to identify and validate ALS biomarkers.
• AI-Driven Early Diagnosis: Use of AI and NLP for automated extraction of early clinical features from EHRs, speech and language analysis, or fluid biomarker or imaging data to improve early detection of ALS.
• Pathomechanistic Knowledge Graphs: Integration of NLP tools with the published medical literature for discovery of previously underappreciated mechanistic targets.
• Disease Progression Modeling: AI-based analysis of longitudinal clinical and /or biomarker data to enhance prediction models for disease progression and stratification of patients.
• Optimizing Clinical Trials: AI-powered patient stratification, automated NLP-based extraction of clinical endpoints from records, virtual comparison groups and trial recruitment optimization.

Data Subtypes: Use of AI technology to separate ALS from Controls and to find ALS subtypes in the Answer ALS data set by combining clinical, biomarker, genetic and motor neuron omics data.

Eligibility Criteria:

• Open to researchers at academic, medical, and research institutions worldwide.
• Multidisciplinary and collaborative proposals integrating AI/NLP expertise with ALS clinical or biological research are encouraged.
• Prior AI/NLP experience is not required, but partnerships with computational experts are recommended.

Pharmaceutical & Clinical Collaboration: Synergistic collaboration between industry and institutions with data-driven models encouraged

Funding and Award Information:

• Grant Duration: Up to 2 years
• Funding Amount: Up to $400,000 USD total (inclusive of both direct and indirect costs)
• Number of Awards: 3 awarded teams
• Indirect Costs: Maximum of 15%

Application Timeline:

• Initial Letter of Interest (LOI) Submission Deadline: Friday May 23, 2025
• Notification of LOI Submission: July 2025
• Full Proposals Due: Wednesday August 6, 2025
• Project Start Date: Wednesday October 1, 2025

Review Criteria:

Proposals will be evaluated based on:

1. Scientific Merit and Innovation: Potential of AI/NLP methodologies to transform ALS research.
2. Feasibility and Approach: Strength of study design, methodology, and data integration strategy.
3. Investigative Team: Expertise and collaborative potential of the research team.
4. Translational Potential: Likelihood of findings contributing to improved ALS diagnostics, treatments, or patient outcomes.

How to Apply:

Application Process

This will be a two-step process. Applicants will first submit a formal Letter of Interest. Selected applicants will then be asked to submit a full proposal if chosen.

1. First Step – Letter of Intent:

Letter of Intent should be max 2 pages in length and include the following:

• • Proposal Title
  • Team’s highlighted experience
  • Brief overview of project
  • Expected Outcomes

2. Second Step – Expanded Application

• If Letter of Interest is accepted, you will be asked to provide a cover letter addressed to ALS Finding a Cure and the Leandro P. Rizzuto Foundation including:
  • Proposal Title
  • Total costs (15% overhead cap)
  • Number of milestones and related costs (to equal amount above)
  • List of all investigators and institutions
  • Name and contact information for person(s) responsible for contracts
  • Address for mailing of payments
• Provide a study plan including:
  • A brief abstract suitable for media release to the lay public if the application is successful
  • Project Plan, Background, and Timeline (max. 5 pages) including:
  • Study background and rationale/significance
  • Study objectives/specific aims
  • Supporting/preliminary data;
  • Experimental design/research plan;
  • Source of data and confirmation of access;
  • Detailed itemized budget and budget justification
  • Description of study milestones, including the costs associated and timeline of specific deliverables
  • Any research funding from other funding sources that relates to the proposed work
• Signed and dated investigator CVs
• Financial Disclosure Form: use either NIH form https://ethics.od.nih.gov/forms450 ), or institutional form.

Submit LOI to: https://app.box.com/f/33b7d67838bb4bc987eb5e65686411ea

Please submit questions to info@alsfac.org

ALS Finding a Cure^® is committed to supporting cutting-edge research that will drive meaningful advancements in ALS discovery through AI and NLP.

Our Pals for pALS Community Connect Program

One of the greatest wishes of our founder, Kevin Gosnell, after launching ALS ONE and united research and care—and before losing his battle to ALS just 14 months after his diagnosis—was to build a compassionate, connected community for those impacted by the disease. He envisioned a network where individuals living with ALS, those who had lost loved ones, and supporters could come together to uplift one another, easing the journey with shared understanding, support, and even moments of joy.

Our Pals for pALS program brings this vision to life by creating a structured way for our incredible community to connect. While many of these relationships have formed organically, this initiative provides an accessible platform to foster even deeper connections.

Pals for pALS is unique in its kind, uniting families currently navigating ALS with a vast network of resilient, kindhearted individuals who have faced the challenges of the disease firsthand. Whether through offering guidance, emotional support, help with chores, or simply being a companion along the journey, participants share their experiences to ensure that no one faces ALS alone.

Additionally, this program strengthens bonds among those affected—whether individuals with ALS, caregivers, children, or extended family members—helping them find solace in shared experiences. By alleviating isolation and providing meaningful support, Pals for pALS creates a true community of care, compassion, and connection.

We are so grateful to have been named a recipient of the ALSFAC We-Care grant to help expand this program to help all and ensure that no one travels the ALS journey alone.

www.alsone.org

Hope Loves Company (HLC) is a nationally recognized nonprofit that provides support, resources and community to children who have or had a loved one with ALS. We give children and young adult caregivers the tools they need to navigate grief, find joy, and remain hopeful.

Recognizing a gap in support services for young caregivers, Jodi O’Donnell Ames founded HLC to provide critical emotional and educational resources for children and young adults. HLC’s focus is to offer mental health and educational support and caregiving resources through free, year-round, nationwide programs, including Camp HLC, Hugs of Hope, Beyond the Bunk hangouts and more.

ALS Finding a Cure and Hop On A Cure announce their partnership to award $1.5M in grant funding for 2-year awards designed to advance the application of organoid technology for use in ALS translational research and development.

Organoids are a powerful new and compelling technology for studying disease biology. Several different and complementary organoid models currently exist with relevance to ALS, but none of these models has been tested across multiple ALS iPSC lines, and all have been created using different lines/genetic backgrounds making comparisons between/among them challenging. The reagents and assays used to assess ALS phenotypes have likewise varied. This variability and limited scale make it challenging to interpret results and to establish methodologic robustness.

ALS Finding a Cure recently issued a grant call for proposals with the following goals:

1. To enable direct comparison of results of multiple organoid methods by providing the same starting materials (iPSC lines) and reagents (antibodies) at scale
2. To identify methods that generate organoids showing key ALS phenotypes
3. To develop robust and reproducible methods that could be used for drug screening
4. To foster collaboration and sharing across organoid model developers to identify best practices, commonalities, and differences across methods

Proposals were reviewed by an international review committee compromised of members from academia, industry, and the non-profit sector, and 5 proposals will receive funding. The teams will work together to share methodology and results.

The projects include:

1) Longitudinal characterization of reproducible ALS phenotypes in iPSC-derive sensorimotor organoids (Joao Pereira Ph.D. – University of Alabama at Birmingham)
2) Benchmarking region-specific organoids and cortico-motor assembloids to study ALS (Jimena Andersen, Ph.D. and Jie Jiang, Ph.D. -University Emory University)
3) Probing consistent and reproducible pathophysiological phenotypes in the novel forebrainspinal circuitoid models derived from ALS patients (Liang Oscar Qiang, M.D./Ph.D. and Daryl A. Bosco, Ph.D. -University Drexel University and UMass)
4) Characterization of the human ALS motor neuraxis organoid system for disease-modeling (András Lakatos, Ph.D. – University of Cambridge, UK)
5) A novel human cortico-spinal assembloid model of ALS/FTD (Kornelia Szebenyi, Ph.D. -University HUN-REN Research Centre for Natural Sciences, Hungary)

Deepti Lall, PhD and Clive Svendsen, PhD at Cedars Sinai will coordinate the distribution of cell lines and reagents.

For further information please contact: info@alsfac.org

About ALS Finding a Cure®

ALS Finding a Cure® (ALSFAC), is focused on identifying gaps in the scientific understanding of ALS that are preventing the development of a cure. The organization, a program of The Leandro P. Rizzuto Foundation, collaborates with numerous companies, ALS organizations, and pALS (people with ALS) and their families to ensure research efforts are non-duplicative, synergistic, and focused on the ultimate goal: finding a cure.

About Hop On A Cure

Hop On A Cure started in 2022 after John Driskell Hopkins of Zac Brown Band was diagnosed with ALS. ALS is consistently one of the most underfunded diseases for research. Because of that, not much significant progress has been made since Lou Gehrig passed away from the disease in 1941. The mission of the foundation is to support research to prevent, reverse, and cure ALS while raising awareness, building a compassionate community, and unleashing the healing power of hope. For more information about Hop On A Cure visit www.hoponacure.org.

Compassionate Care ALS (CCALS), a nonprofit located in Falmouth, Massachusetts, currently works with more than 1,050 ALS families in 47 states and multiple foreign countries.  Funding from ALSFAC WE CARE will allow CCALS to grow its staff to serve more ALS patients their families, communities, and healthcare providers.  We will provide resources including equipment, educational opportunities, Medicare/Medicaid assistance, communication assistance, guidance and awareness with regards to living with ALS, caregiving, and exploring end-of-life when invited, all at no cost to families across the United States.

As a patient-driven, primarily volunteer organization, the mission of ALS Ride For Life is to serve the ALS community by assisting patients and their families through a variety of supportive services to ease the financial and emotional stress this disease places on families, raising research funds to find a cure, raising public awareness, and providing the community with the latest ALS news, information, and inspiration. With a minimal staff (the equivalent of 2 employees), an active board of directors, and a team of volunteers.

To apply for our Mobility Matters Program or one of our other grants, follow this link: https://alsrideforlife.org/programs-assistance/

Overview:

Organoids are a powerful new and compelling technology for studying disease biology. Several different and complementary organoid models currently exist with relevance to ALS, but none of these models has been tested across multiple ALS iPSC lines, and all have been created using different lines/genetic backgrounds making comparisons between/among them challenging.

The reagents and assays used to assess ALS phenotypes have likewise varied. This variability and limited scale make it challenging to interpret results and to establish methodologic robustness.

This targeted RFP aims to answer the question: are there reproducible ALS phenotypes (pathology, omics, biomarkers) that are detectable within and/or across organoid models created from human C9orf72 and TDP43 mutation-carrying lines that differ from organoids derived from healthy gender and age-matched controls.

We are specifically looking for reliable ALS-relevant phenotypes that are widely observed (regardless of which line was used), reproducible, easily measured, and appear as early as possible, so as to potentially enable humanized disease modeling and utility for future therapeutic development.

We are ideally looking for assembloid models incorporating corticospinal motor neurons, spinal motor neurons, and muscle cells, so as to form a true ALS “circuit”, but will also consider applications utilizing any two out of these three cell types/regions. In addition to the “required” cell types, groups are also encouraged to incorporate multiple additional cell types, including glial cells, into their organoid models so as to more faithfully recapitulate the full extent of disease biology.

At the end of the grant period, we plan to invite all the funded labs back together for a follow- up workshop to compare methodologies, share data, discuss technical challenges, and brainstorm ideas for next steps. We encourage collaborative proposals and are hoping to fund a

diverse range of models/methods so as to accelerate the field. Experience developing organoids and compelling preliminary data will be important criteria for the review committee.

Materials Provided:

We will provide funding for proposals to develop organoids from 5 male C9ORF72 ALS and 5 age-matched control iPSC lines from the Answer ALS cohort, 1 C9orf72 ALS and 1 matching revertant control line, and 1 M337V line and 1 matching wild type/revertant control line from the INDI cohort, all at similar passage numbers. This will allow everyone to compare the phenotypes in their models based on identical lines. All lines will be provided to groups in a blinded fashion to better enable validation of independent approaches.

Where possible, funded labs will also be provided with standardized antibodies for the following:

• p-TDP43
• C and N-terminal TDP43
• DPR analysis will be performed at Mayo Clinic using the antibodies developed by Dr. Len Petrucelli’s group

Outcome Measures:

There are two key measures of success we would like the funded labs to address: maturational state and demonstration of ALS-relevant pathophysiology.

Cellular Maturation (proof of basic biology):

• Transcriptomic signatures (groups are encouraged to perform both snSEQ and bulk RNA transcriptomic analyses if possible)
• Please provide information as to the maturation state of the cells in your organoid models via at least 1 of the following immunohistochemical markers:
  1. ChAT expression
  2. UCHL1 expression
  3. GFAP expression
  4. Markers of NMJ maturation/innervation (for those organoid models that include muscle)
• Please provide information as to the maturation state of the cells in your organoid models via at least 1 of the following functional assessments:
  1. Electrophysiologic measures of cellular activity

1. Calcium imaging of cellular activity
2. Ability to drive muscle fiber contraction via stimulation of connecting neurons (for those organoid models including muscle)
3. Measures of synaptic density
4. Other functional assessments

Recapitulation of ALS phenotypes (necessary for translation):

1. Validation of DPR production in the C9 When do DPR’s appear? Which DPR’s?
2. Accumulation of RNA foci in the C9 Which cell types do you see foci in? What % of cells show foci? How many foci on average are there per cell? What is the earliest timepoint for reliable detection of foci?
3. Are you able to detect translocation of TDP43 out of the nucleus of corticospinal motor neurons and/or spinal motor neurons in your organoid models? If so, what is the earliest timepoint for reliable detection?
4. Are you able to detect other signs of TDP43 dysfunction in your models (changes in transcriptomics, presence of cryptic exon inclusion/splicing defects, etc)? If so, what is the earliest timepoint for reliable detection?
5. In those C9 and TDP43 derived organoids which include muscle, are you able to detect changes in NMJ’s? (numbers, size, innervation status, electrophysiological responses, etc) If so, what is the earliest timepoint for reliable detection?
6. Are you able to detect other signs of neuropathology in your organoid models? (e.g. cell death, inflammation, synapse loss, axonal changes, etc) If so, what is the earliest timepoint for reliable detection? We suggest using both an NFL assay and an LDH release assay to measure differences between ALS and control

Funding Timelines:

Applications open: November 20th, 2023 Applications due: January 31st, 2024 Anticipated earliest start date: June, 2024 Submit to: https://app.box.com

Grants are for the support of 2-year proposals of up to $300,000 USD total (inclusive of a maximum of 15% in indirect costs). Costs for lines and antibodies will be contracted separately by ALS Finding a Cure (and do not need to be included in the requested budget). Support will not normally exceed 2 years and applicants should submit proposals that are compatible with a 2-year time frame. The continuation of funding within this period will be subject to the submission of satisfactory progress reports, which will be required at six-month intervals.

Application Process

1. Please provide a cover letter addressed to ALS Finding a Cure and the Leandro Rizzuto Foundation including:
   1. Proposal Title
   2. Total costs (15% overhead cap)
   3. Number of milestones and related costs (to equal amount above)
   4. List of all investigators and institutions (and letters of collaboration if external to the PI’s lab and institution)
   5. Name and contact information for person(s) responsible for contracts
   6. Address for mailing of payments
2. Provide a study plan including:

• A brief abstract suitable for media release to the lay public if the application is successful
• Project Plan, Background, and Timeline (max. 5 pages) including:
  • Study background and rationale/significance
  • Study objectives/specific aims (i.e. how you plan to address the success measures outlined above in the RFP)
  • Supporting/preliminary data;
  • Experimental design/research plan;
• Detailed itemized budget and budget justification
• Description of study milestones, including the costs associated and timeline of specific deliverables
• Any research funding from other funding sources that relates to the proposed work

3. Signed and dated investigator CVs
4. Financial Disclosure Form: use either NIH form https://ethics.od.nih.gov/forms450, or an equivalent institutional form.