Tambourine Philanthropies, the philanthropic initiative of Ben and Divya Silbermann, has partnered with SPARC since 2021 to analyze and understand the amyotrophic lateral sclerosis (ALS) research ecosystem and identify where philanthropic investments could be deployed to overcome barriers to scientific progress.
ALS Breakthrough Research Fund
Tambourine’s ALS Breakthrough Research Fund was designed to change scientific understanding and improve the treatment of ALS by supporting innovative basic and discovery-focused research globally. Drawing inspiration and drive from the founders’ family experience with ALS, Tambourine is committed to enabling breakthrough scientific discoveries and attracting new ideas, talent, and tools that lead to better diagnoses, treatments, and cures for ALS.
The fund particularly focuses on funding creative, high-risk, high-reward, and innovative discovery-driven research proposals that might not otherwise fit existing grant programs:
ALS Breakthrough Research Fund Awardees: Tambourine has committed more than $5 million to eight research teams selected from the ALS Breakthrough Research Fund’s 2023 Request for Proposals (RFP). Projects run for 2–3 years.
The RFP focused on exciting and foundational scientific directions that can shed light on ALS mechanisms, sporadic ALS, and non-inherited contributions to disease.
All submitted proposals underwent rigorous peer review by an external panel of experts. Proposals were assessed against several criteria specified in the RFP. The ALS Breakthrough Research Fund’s scientific leadership—including the Scientific Advisory Board—used scientific review feedback in tandem with the fund’s strategic direction in making funding recommendations to Tambourine.
To date, eight research teams have been awarded grants to conduct basic and discovery-focused research aiming to change how we understand and treat ALS.
Scientific Priorities & Funding Details
Investigating ALS Disease Mechanisms
Use novel tools and approaches to uncover fundamental biological processes driving ALS.
Decoding Sporadic ALS
Identify molecular pathways and pathological features underlying non-familial forms of ALS
Exploring Non-inherited Contributors
Study epigenetics, environmental factors, and gene-environment interactions in ALS development
Pursuing High-Risk, High-Reward Ideas
Propose bold, creative research directions that may not qualify for traditional funding
Leveraging Cross-Disciplinary Expertise
Apply tools and insights from adjacent diseases and fields (e.g., data science, neurodegeneration) to ALS discovery science
Funding Details for Awards
Eight two-year research grants were awarded in early 2024.
Grants are up to $600,000 in funding over two years, inclusive of indirect costs.
An optional third year of funding will be available for projects that merit continued support.
Scientific Advisory Board
SteveFinkbeiner, MD, PhD
Director, Center for Systems and Therapeutics and the Taube/Koret Center for Neurodegenerative Disease Research at Gladstone Institutes
ShaneLiddelow, PhD
Assistant Professor, Department of Neuroscience and Physiology at the NYU Grossman School of Medicine
ClotildeLagier-Tourenne, MD, PhD
Associate Professor of Neurology, Massachusetts General Institute for Neurodegeneration
DianeRe, PhD
Assistant Professor, Environmental Health Sciences at the Columbia University School of Public Health
Awardees and Projects
Project
Decoding the role of microglia in motor neuron selective vulnerability in Amyotrophic Lateral Sclerosis
Bahareh Ajami, PhDOregon Health Science University, Oregon, US
Overview
This project aims to use state-of-the-art approaches for examining gene expression profiles and cellular connections. The objective is to uncover the mechanisms underlying the differential vulnerability of various motor neuron populations to degeneration in ALS. These studies will generate a valuable dataset that other researchers can learn from and interrogate, promote further understanding of the role of microglia in preserving motor neuron health, and unveil novel therapeutic strategies.
Project
Understanding ALS mechanisms in a novel human cellular model of the cortico-motor pathway
Jimena Andersen, PhDEmory University
Overview
This project aims to develop cutting-edge 3D cellular models that recapitulate the connection between the brain, spinal cord, and muscles of ALS patients. The team will use these novel models of ALS to compare the cellular composition, gene expression profiles, and genetic susceptibility of ALS-affected and unaffected cellular networks. Overall, these studies will generate a new ALS model using human cells that could be transformative for studying mechanisms underlying ALS and developing novel therapies.
Project
VAPB and membrane contact sites in amyotrophic lateral sclerosis (ALS) pathogenesis
Marianna Leonzino, PhDIRCCS Humanitas Research Center
Co-Investigator: Paolo Colombi, PhD, Istituto di Genetic Molecolare
Overview
This project aims to employ innovative technologies to better resolve the function and composition of cellular components that serve as a convergence point of pathogenic pathways involved in familial and sporadic ALS. This project could uncover a molecular pathway that unifies several subtypes of ALS under one molecular process, transforming how science thinks about ALS and discovering a compelling therapeutic target at the same time.
Project
Linking TDP-43 pathology to synaptic (dys)function in ALS and FTD
Magdalini Polymenidou, PhDUniversity of Zurich
Co-Investigator: Martin Muller, PhD
Overview
This project aims to mechanistically resolve a critical knowledge gap regarding the functional impact of pathological aggregation of TDP-43 protein on the structure and function of synapses. This project will provide greater insight into how one of the key molecules involved in ALS and frontotemporal dementia (FTD)—TDP-43—leads to a breakdown of cellular communication within the brain, thus yielding mechanistic insights that cut across multiple neurodegenerative diseases.
Project
Disentangling circuit mechanisms of cortical hyperexcitability in ALS towards the discovery of novel diagnostic tools and therapeutic approaches
Caroline Rouaux, PhDInserm and Strasbourg University, France
Co-Investigator: Sabine Liebscher, MD, PhD, University of Cologne and University Hospital Cologne, Germany
Overview
This project aims to use a novel approach in human tissue and rodent models to test the hypothesis that hyperexcitability of the motor cortex can serve as a diagnostic and prognostic biomarker in ALS. It will also probe the utility of correcting noradrenaline activity in the brain as a therapeutic method. This project has a clear translational impact as it pursues the development of biomarkers and identifies a potential new target for early intervention or treatment of ALS.
Project
Using sporadic ALS patient-derived motor neuron cultures to resolve molecular subtypes and discover new therapeutics
Clive Svendsen, PhDBoard of Governors Regenerative Medicine Institute, Cedars-Sinai
Co-Investigator: Earnest Fraenkel, PhD, Massachusetts Institute of Technology; Michael Workman, PhD, Cedars-Sinai Medical Center
Overview
This project aims to reveal specific molecular signatures and subtypes of ALS by combining gene expression profiling, robotic imaging, and advanced artificial intelligence methods with patient-derived motor neurons. These studies could effectively subtype people living with ALS and enable precision medicine treatment approaches. This project leverages the powerful, open-access biological resources developed through the Answer ALS research project to develop a novel platform for resolving the heterogeneity of sporadic ALS at the cellular level.
Project
A systemic dissection of the interaction between sporadic ALS risk genes and environmental factors
Ryan West, PhDSheffield Institute for Translational Science, the University of Sheffield
Co-Investigator: Jonathan Cooper-Knock, PhD, Sheffield Institute for Translational Science, the University of Sheffield, England
Overview
This project aims to mechanistically test the hypothesis that combinations of genetic mutations create a predisposition to environmental risk factors, leading to sporadic ALS. The team will combine predictive computer modeling—using data from the large, open-access genetic dataset Project MinE—with mechanistic, experimental manipulation of genetic and environmental factors. These studies will help us understand the commonalities and specific risk factors for sporadic ALS, which have proven difficult to identify.
Project
Modulation of protein surveillance mechanisms in sporadic and familial forms of ALS
Hynek Wichterle, PhDColumbia University
Co-Investigator: Emily Lowry, PhD, Columbia University
Overview
This project aims to conduct a detailed, mechanistic study of the critical cellular processes that break down proteins and test the therapeutic potential of compounds targeting these protein-degradation mechanisms. This discovery-focused study could help identify new therapeutic targets and generate new hypotheses about the role of impaired protein breakout in neurodegenerative disease.
SPARC and Tambourine Philanthropies partnered to analyze ALS funding and research. This guide pinpoints where focused philanthropy can accelerate progress.
