The Edward Asten Foundation drives translational neuroscience research, expands access to clinical trials, and delivers direct support for patients living with ALS and motor neuron disease.
The Edward Asten Foundation is organized and operated exclusively for charitable, scientific, and educational purposes under Section 501(c)(3) of the Internal Revenue Code. We exist to accelerate development of disease-modifying therapies, expand access to clinical trials, provide direct patient support, and build a self-sustaining funding ecosystem for neurological research — one that does not depend on donations alone.
ALS is a progressive, fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons, leading to muscle weakness, paralysis, and respiratory failure. Median survival remains 2–5 years from symptom onset. Currently approved therapies provide only modest benefit. The work cannot wait.
ALS is a multifactorial neurodegenerative syndrome. Approximately 90% of cases are sporadic; ~10% are linked to genetic mutations. EAF research spans the full continuum — from fundamental disease biology and biomarker discovery to clinical trial execution and real-world patient access.
TDP-43 cytoplasmic aggregation and nuclear depletion is present in over 95% of ALS cases, disrupting RNA metabolism and triggering neuronal toxicity. Mutant SOD1 causes structural instability and toxic gain-of-function, producing oxidative stress and motor neuron death. Aberrant cytoplasmic inclusions of misfolded proteins are a defining hallmark of ALS pathology.
TDP-43 dysfunction causes cryptic exon inclusion and RNA splicing abnormalities, leading to progressive loss of neuronal function. C9orf72 GGGGCC hexanucleotide repeat expansions — the most common known genetic cause of ALS — further dysregulate RNA metabolism and are present in approximately 40–50% of familial ALS cases.
Glial activation, mitochondrial dysfunction, impaired axonal transport, oxidative stress, excitotoxicity, and synaptic degeneration at the neuromuscular junction are all active EAF research targets. Neuroinflammation involving activated microglia is observed across both familial and sporadic ALS cases.
C9orf72 expansions account for ~40–50% of familial ALS. SOD1 mutations are present in ~20% of familial and ~2% of sporadic cases. TDP-43 pathology is observed in over 95% of all ALS cases regardless of genetic status.
EAF prioritizes therapies that intervene at the genetic, molecular, cellular, and delivery level. A critical challenge across all therapeutic modalities is crossing the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) to reach motor neurons — a problem that has historically limited conventional drug delivery in ALS. Each program is grounded in peer-reviewed science and oriented toward clinical translation.
Messenger RNA lipid nanoparticle (mRNA-LNP) therapy is an emerging and potentially transformative platform for ALS. The central challenge in ALS drug delivery is the blood-brain barrier — a highly selective vascular barrier with tight junctions between endothelial cells that blocks nearly all protein-based and large-molecule therapies from reaching motor neurons. The blood-spinal cord barrier (BSCB) presents an additional obstacle that conventional drug delivery systems cannot reliably overcome.
Lipid nanoparticles (LNPs) are nano-scale fatty droplets that encapsulate mRNA or other therapeutic molecules, are introduced into the bloodstream, and are absorbed by cells — at which point the LNP dissolves and the mRNA begins producing its target protein. This technology was validated at scale by the mRNA COVID-19 vaccines. However, those LNPs were not engineered to cross the BBB. EAF supports the development of next-generation BBB-penetrating LNPs specifically designed to deliver therapeutic payloads directly to neurons in the brain and spinal cord.
Once a BBB-crossing LNP platform is established, it becomes what researchers describe as a plug-and-play delivery system: the same vehicle can carry mRNA for protein replacement therapy, siRNA to silence toxic mutant proteins, or CRISPR-Cas9 guide RNA to permanently edit out deadly mutations such as those caused by C9orf72 or SOD1. The delivery vehicle is target-agnostic — solving it once unlocks many therapeutic possibilities simultaneously. This will represent the first time an mRNA-LNP therapeutic has been evaluated for ALS.
Current research is evaluating LNP transport across model BBB systems with neuronal cells, identifying candidates that efficiently cross the vascular barrier and transfect neurons — with parallel development of specific mRNA constructs targeting TDP-43 biology and C9orf72 biology.
Deliver mRNA instructing neurons to produce a missing or healthy protein in place of a mutant form
Deliver siRNA to suppress toxic mutant protein expression in SOD1 or C9orf72 ALS
Deliver mRNA + guide RNA to permanently edit out mutations causing ALS at the genomic level
Single delivery system adaptable to any new protein target as the research community identifies them
Wang et al., Materials Today Bio, 2020 (PMC7280770) · ALS TDI / Mitchell Lab, Univ. of Pennsylvania, 2026
EAF supports the full spectrum of RNA-targeted interventions, including antisense oligonucleotides (ASOs), siRNA, and CRISPR-based gene editing platforms. Clinical validation has already arrived: Tofersen (FDA-approved 2023) is an ASO that reduces SOD1 protein production by targeting SOD1 mRNA. In the VALOR trial, Tofersen produced significant reductions in CSF SOD1 protein, decreased neurofilament light chain (NfL), and demonstrated slowed disease progression with early treatment — confirming that ALS can be treated at the gene-expression level. An ASO targeting C9orf72 repeat expansions (BIIB078) has entered Phase I clinical trials. These results validate RNA-targeted therapeutics as a major pathway forward and establish the scientific basis for EAF's broader gene therapy programs.
Miller et al., NEJM 2022 · VALOR Trial (NCT02623699) · Tofersen FDA approval 2023
EAF supports responsible investigation of neural stem cell transplantation, induced pluripotent stem cell (iPSC) models, and glial cell modulation — targeting astrocytes and microglia. The biological goals are to restore neurotrophic support to surviving motor neurons, reduce neuroinflammation, and stabilize or replace degenerated cells. Mesenchymal stem cells (MSCs) offer particular promise: they can support motor neurons, reduce inflammation, stimulate tissue regeneration, and release growth factors — and their secreted extracellular vesicles may provide therapeutic benefit without the full challenges of direct cell transplantation. iPSC-derived motor neuron models also serve as critical research infrastructure for drug screening and target validation.
Kwon et al., Nature Medicine 2022 · Bonafede & Mariotti, Front. Cell. Neurosci. 2017
EAF supports engineered peptide therapeutics — short chains of amino acids carrying precise molecular instructions for target-specific biological activity. Applications include protein folding modulation, neuroprotection, and targeted intracellular signaling. These are precision biologics operating at the level of pathological protein aggregation, and are entirely distinct from metabolic or weight-management peptides. Recent research has identified small molecules and peptides capable of directly inhibiting SOD1 and TDP-43 aggregation — presenting a direct modulation strategy that complements gene-based approaches and represents a rapidly advancing class of ALS therapeutics with growing preclinical evidence.
PMC11157337 — SOD1 and TDP-43 aggregation inhibitors, 2024
Modern ALS trials depend on quantifiable biomarkers for early diagnosis, patient stratification, and objective measurement of treatment response. FDA acceptance of neurofilament light chain (NfL) as a surrogate endpoint marks a critical regulatory advancement — enabling smaller, faster, and more efficient clinical trials.
Neurofilament light chain (NfL) — marker of axonal injury; FDA-accepted surrogate endpoint in ALS trials; measurable in both CSF and blood
CSF SOD1 protein — quantifiable target validated by the VALOR trial as a direct measure of gene-silencing therapy efficacy
TDP-43 cryptic peptides — emerging biomarker for RNA splicing dysfunction detectable in CSF as disease progresses
Multi-omics platforms — integration of genomics, proteomics, and transcriptomics to enable precision patient stratification
Electrophysiological metrics — motor unit number estimation and nerve conduction studies as objective functional biomarkers
Longitudinal biofluid repositories — CSF and blood sample banks enabling biomarker discovery across disease stages and genetic subtypes
Reproducible, collaborative science requires shared infrastructure. EAF supports development of the tools the field needs to move faster.
Longitudinal CSF and blood biofluid repositories, postmortem tissue programs, and iPSC stem cell libraries to accelerate target discovery and drug validation.
Development and sharing of validated antibodies, animal models, and integrated data platforms to improve reproducibility and collaboration across the ALS research community.
EAF supports open data standards and pre-competitive research sharing — removing barriers to discovery that arise when critical findings remain siloed within individual institutions.
Advanced ALS often renders long-distance ground travel medically impossible. Ventilator-dependent, wheelchair-bound patients cannot tolerate the logistical demands of road transport. EAF provides free medical air transport to ALS patients and paralyzed veterans — enabling access to clinical trials, specialist centers, and advanced care anywhere in the country.
To build this program, EAF is actively seeking donated aircraft that meet our mission profile: reliable, cost-efficient platforms with wide flat-floor cabins that can be fully reconfigured for any level of medical need — from ambulatory patients to ventilator-dependent individuals requiring ICU-level support. Aircraft are selected for proven dispatch reliability, low operating cost (under 300 gal/hr in cruise), and wide-body flat-floor cabin accessibility.
Pilatus PC-12
Turboprop · flat floor · unpaved capablePilatus PC-24
Light jet · short field performanceCirrus Vision SF-50
VLJ · low operating costBeechcraft King Air 250 / 260
Twin turboprop · proven dispatch recordBombardier Challenger 604 / 605 / 650
Wide cabin · long rangeBombardier Challenger 350 / 3500
Super midsize · excellent reliabilityDassault Falcon 2000 / 6X / 8X
Wide cabin · intercontinental rangeMission requirement
Under 300 gal/hr cruiseAll operations
FAA CFR FAR Part 135 certifiedOwn or have access to an aircraft that fits this profile? Donating an aircraft to EAF is a tax-deductible contribution. Your gift directly enables free medical flights for ALS patients and paralyzed veterans who cannot travel by ground. Contact us to discuss an aircraft donation →
EAF fields dedicated government affairs teams working directly with members of Congress and federal agencies. We do not wait for policy to catch up to the science — we drive it.
Increased NIH and DoD ALS program appropriations. Accelerated FDA approval pathways for motor neuron disease therapies. Expansion of ALS-specific clinical trial infrastructure and geographic access to trials.
Coverage for advanced ALS therapies, durable medical equipment, non-invasive ventilation systems, assistive communication technologies, long-term caregiving, and multidisciplinary treatment teams.
EAF provides financial assistance, patient navigation and consulting, insurance advocacy, and coordination with ALS specialty clinics. Our goal is to eliminate the bureaucratic and financial barriers that stand between a patient and the care they need.
Financial assistance for patients and families facing the cost of ALS care, equipment, and caregiving
Patient navigation through clinical trial enrollment, specialist referrals, and multidisciplinary care coordination
Insurance advocacy to secure coverage for advanced therapies, ventilation systems, and durable equipment
Veteran support — dedicated services and free air transport for paralyzed veterans seeking specialized care
EAF is designed to generate its own revenue over time, reducing dependence on external donations. FAA Part 135 charter operations, air ambulance contracts with hospitals and insurers, and organ transport partnerships feed directly into research funding. All net revenue is reinvested into research, clinical trials, and patient programs.
The Edward Asten Foundation is currently pending 501(c)(3) nonprofit approval from the IRS. Once approved, online donations — including monthly recurring giving — will be available here. Every dollar raised will go directly toward neurological research, patient support, and policy advocacy.
Want to be notified when donations open? Reach out to us directly and we will contact you as soon as our 501(c)(3) status is confirmed and the donation portal is live. No patient should face ALS without hope — or without access to care.
info@edwardastenfoundation.org →