Bringing the ALS Research Community Together
This year’s event brought together over 1,000 researchers, clinicians, industry partners, non-profit collaborators, and people living with ALS to share knowledge, collaborate, and honor the strength of our community. We were especially excited to have a record-breaking 214 accepted abstracts this year. Additionally, we featured more science than ever before with the introduction of our Lightning Science Talks, which offered a dynamic new way to highlight cutting-edge research.
For the first time, Annual NEALS Meeting participants were able to earn CME credits by participating in the Respiratory Care & Ventilation Committee Workshop organized by the NEALS Respiratory Care & Ventilation Committee, chaired by Drs. Eufrosina Young (SUNY Upstate Medical University), Benjamin Rix Brooks (Clinical Trials Planning LLC), and Christopher Lee (Vanderbilt University Medical Center). In addition, NEALS members benefited from a range of exclusive professional development opportunities, including the newly revamped Clinical Research Staff Training & Development Workshop, Outcome Measures Training, and Feeding Tubes and ALS: Multidisciplinary Practical Considerations Workshop, led by the NEALS Bulbar, Respiratory Care & Ventilation, Palliative, and Nutrition Committees.
Participants who successfully completed the Clinical Research Staff Training & Development Workshop, led by members from the Healey & AMG Center for ALS at Mass General and Barrow Neurological Institute, received a certificate of completion, recognizing their commitment to upholding high standards in clinical research management.
The Annual Meeting continues to provide NEALS members with exclusive educational programs designed to empower them to conduct rigorous clinical trials and advance ALS research. As always, our NEALS committee meetings served as a cornerstone of collaboration and progress across the consortium.
Drs. Suma Babu (Healey & AMG Center for ALS at Mass General) and Björn Oskarsson (Mayo Clinic) led an engaging session on Learnings from EAPs in ALS, open to all attendees, and we were honored to welcome Dr. Claire Clelland as this year’s keynote speaker, presenting Updates on Developing CRISPR Gene Therapy for C9orf72 FTD/ALS.
Advancing Science, Partnership, and Patient Engagement Across Sessions
The pillars of this year’s meeting reflected NEALS’ commitment to advancing science, partnership, and patient engagement. Attendees heard about ongoing and emerging clinical research and trials during the NEALS Affiliated Trial Session; explored collaborative innovation at the Industry Roundtable; and were inspired by the Research Ambassadors Driving Change session. Additional highlights included the Science Symposium: Innovative Approaches and Future Directions for Treating Sporadic ALS, Stats Corner: Small Trials, Big Decisions in Early Phase ALS Research, and our Platform Presentations showcasing the best of NEALS science.
New this year was Uniting for Impact: Updates from the NEALS ALS Organizations Forum, featuring updates from our community partners and demonstrating the collective impact of collaboration across the ALS ecosystem.
NEALS at 30: Honoring a Legacy, Inspiring the Future
This was a particularly meaningful year as we commemorated NEALS’ 30th anniversary with a special Opening Session: NEALS at 30 – A Legacy of Impact. Founded by Dr. Merit Cudkowicz (Healey & AMG Center for ALS at Mass General) and Dr. Jeremy Shefner (Barrow Neurological Institute), NEALS has grown over three decades into a leading collaborative network dedicated to advancing ALS research, now encompassing over 160 sites. Today, under the leadership of current Co-Chairs Dr. Jinsy Andrews (New York University) and Dr. James Berry (Healey & AMG Center for ALS at Mass General), NEALS continues to drive innovation and partnership across the ALS community. Click here to watch the NEALS 30th Anniversary video.
We’re also excited to share that NEALS has a new name: the Network of Excellence for ALS. This change reflects what NEALS has become — a global network of researchers, clinicians, and people living with ALS, all working together to accelerate the discovery and delivery of effective treatments. NEALS’ rebranding as the Network of Excellence for ALS, underscores its global reach, expanded biorepository capacities, and enhanced training programs designed to cultivate the next generation of ALS researchers and clinicians. While our name has evolved, our mission remains the same: to improve and extend the lives of people living with ALS through collaborative research and education.
Dr. Timothy Miller (Washington University in St. Louis) delivered a powerful talk on ASO Therapies for ALS and shared a moving message of hope, setting an inspiring tone for this milestone year.
We are already looking forward to next year’s meeting—and to seeing how the seeds we planted this year will continue to grow.
We would like to extend our sincere appreciation to our NEALS members who helped capture and share the highlights of this year’s meeting; detailed summaries of each general session follow below. We would also like to thank this year’s sponsors, foundation partners, and government collaborators for their vital support. Their continued investment in NEALS helps sustain the programs, education, and research that drive progress against ALS. We are especially grateful to the ALS Association for sponsoring this year’s beachside dinner, which provided a memorable opportunity for our community to connect and reflect on three decades of collaboration. Together, these partnerships make it possible to convene a global network dedicated to improving the lives of people living with ALS.
Opening Session: A Legacy of Impact – NEALS 30th Anniversary
Written by: Dr. Jennifer Morganroth (Sean M. Healey & AMG Center for ALS at Mass General)
Drs. Merit Cudkowicz and Jeremy Shefner, opened the session with reflections on NEALS’ 30-year journey and a tribute to Layne Oliff, a dedicated PALS advisor. Founded in 1995 by nine New England neurologists, NEALS held its first meeting in March 1996 with a vision to bridge basic science and clinical research. Since then, it has grown into a global network with 165 sites, 80 affiliated trials, and a leading academic CRO. Highlights included more than 50 clinical trials (Topiramate, Creatine, Neudexta, Mexiletine, Amylyx, Tofersen); the Treat ALS and ALS Clinical Research Learning Institute® programs amplifying patient voices; the development of outcome measures and PI training programs; and the creation of the Pro-ACT database and NEALS Biorepository (collecting data from more than 28,000 ALS patients and over 177,000 samples). Fundraising milestones such as the anniversary bike ride from Pittsburgh to DC, which raised $70,000, and blogs by Dr. Jeremy Shefner and Dr. Timothy Miller celebrated the organization’s legacy and community spirit.
Dr. Timothy Miller highlighted advances in antisense oligonucleotides (ASO) therapies for SOD1 ALS, noting early animal studies that doubled survival and the subsequent benefit in human trials. While Tofersen’s Phase 3 trial missed its 28-week primary endpoint, extended results at 52 weeks demonstrated clinical benefit and validated neurofilament light chain (NfL) as a biomarker. Over approximately 2 years, Tofersen reduced NfL levels, suggesting a slowing of the degenerative process, extended survival by roughly 1.6 years in fast progressors, and enabled stabilization or improvement of strength in about 20–25% of patients. Current directions include tofersen use in asymptomatic gene carriers and development of next-generation ASOs targeting other genetic mutations such as C9orf72, Ataxin-2, FUS, Stathmin-2, UNC-122, and SPTLC1.
Driving Progress: Updates from NEALS Affiliated Trials
Written by: Carly Allen (NEALS)
Dr. Jinsy Andrews opened the session with an overview of all NEALS-affiliated trials and Expanded Access Programs, highlighting the consortium’s ongoing commitment to advancing ALS research through collaborative, cutting-edge studies.
Presentations:
Healey ALS MyMatch Program Update
Suma Babu, MBBS, MPH (Sean M. Healey & AMG Center for ALS at Mass General)
EPISOD1 study update on AMT-162 Gene Therapy for Individuals with SOD1 associated ALS
George Apostol, MD (uniQure)
Healey ALS Platform Trial – Adaptations and Next Regimens
Merit Cudkowicz, MD, MSc (Sean M. Healey & AMG Center for ALS at Mass General)
LUMINA Study Update
Lauren Kett, MD, PhD (Amylyx Pharmaceuticals) and Sabrina Paganoni, MD, PhD (Sean M. Healey & AMG Center for ALS at Mass General)
ALL ALS Study Update
James Berry, MD, MPH (Sean M. Healey & AMG Center for ALS at Mass General) and Robert Bowser, PhD (Barrow Neurological Institute)
Industry Roundtable: Partnering to Accelerate ALS Therapeutic Development
Written by: Carly Allen (NEALS)
Moderated by Dr. Nicholas Maragakis (Johns Hopkins University), the Industry Roundtable brought together leaders from pharmaceutical companies to discuss innovative approaches in ALS drug development. Panelists shared insights on investigational products and novel clinical trial designs, as well as strategies for patient recruitment, retention, and subgroup selection. The discussion also explored the integration of biomarkers, trial duration considerations, and the evolving environment for clinical trial execution, including perspectives on Expanded Access Programs (EAP) and Open-Label Extensions (OLE).
Partners in Discovery: Research Ambassadors Driving Change
Written by: Dr. Laura Rosow (University of California, San Francisco)
Drs. Richard Bedlack (Duke University ALS Clinic) and Terry Heiman-Patterson (Temple University) opened Day 2 of the Annual NEALS Meeting with a lively panel discussion featuring three of NEALS' own ALS Research Ambassadors. These ambassadors are all graduates of the Clinical Research Learning Institute® (CRLI) program, an annual, two-day program that provides education and training in clinical research and therapy development to individuals impacted by ALS. The first panelist to speak was Andrea Lyle Peet. A triathlete diagnosed with ALS at the age of 33, Andrea spoke about how she has found exercise profoundly beneficial in her journey with ALS, and she set a lofty goal - which she handily achieved! - to complete 50 marathons in all 50 states following diagnosis. She has become a passionate advocate for the ALS community through Team Drea Foundation, funding ALS research efforts and inspiring PALS to "live bravely, love joyfully, and appreciate the gift of life." The next panelist to speak was John Peffer, who was diagnosed with familial ALS in 2024. John spoke about his background in sales and marketing and his eagerness to apply his specialized expertise to ALS advocacy and fundraising efforts, with several exciting events already planned and a website (with the message to "keep on trucking") in development. He shared his uplifting and honest TikTok channel, where he posts daily videos about his journey with ALS, and he even filmed a TikTok video from the meeting stage - a true NEALS first! Finally, we heard from Jean Swidler, the founder of Genetic ALS & FTD: End the Legacy, a patient-led organization that is dedicated to the needs and interests of the genetic ALS and FTD community. A C9 carrier herself, Jean shared the moving story of how she lost her mother, aunt, and uncle to familial ALS in a short span of time, and how this has helped spark her passionate advocacy for the genetic ALS and FTD communities. Jean has worked tirelessly to improve detection and care for individuals impacted by familial ALS and FTD and is an outspoken advocate for these communities at ALS academic conferences. This was a truly moving and inspiring panel discussion.
NEALS Scientific Symposium Spotlights Bold New Strategies for Tackling Sporadic ALS
Written by: Dr. Amy Chen (University of South Florida) & Dr. Jinsy Andrews (NYU Langone Health)
This year’s NEALS Scientific Symposium, “Innovative Approaches and Future Directions for Treating Sporadic ALS,” led by SAB Co-Chairs Dr. Timothy Miller (Washington University in St. Louis) and Dr. Jeffrey Rothstein (Johns Hopkins University), delivered a fast-moving exploration of the molecular drivers of ALS and the emerging technologies aiming to stop them.
Gene Therapy for Sporadic ALS? A Provocative Opening
Dr. Miller opened the session with a provocative question: Could gene therapies be effective in sporadic ALS (sALS)? Drawing parallels with Alzheimer’s and Parkinson’s disease—conditions where only 5–15% of cases are genetic but share common protein-aggregate pathology—he argued that ALS may similarly benefit from gene-targeted approaches. He highlighted the progress in SOD1-ALS, including the phase 3 Tofersen program and its open-label extension, which together represent one of the strongest demonstrations that targeting a single gene can meaningfully alter disease trajectory.
TDP-43: A Central Target in Sporadic ALS
Dr. Miller emphasized the central role of TDP-43 pathology, present in ~95% of sALS and FTD cases. Discoveries of TARDBP mutations in familial ALS further cemented TDP-43 dysfunction as a core disease mechanism. He showcased emerging assays that probe disease-causing mutations (including those in quaking) and reviewed next-generation strategies for targeting SOD1 and other genetic contributors. His message to the field was clear: methodological rigor and technological refinement will be essential to accelerate therapeutic breakthroughs.
Project Genesis: Mapping ALS Back to Its Earliest Molecular Triggers
Dr. Rothstein introduced Project Genesis, a major initiative aimed at pinpointing the earliest—or “upstream”—events that trigger motor neuron degeneration. Using SOD1-ALS as a model, he contrasted the modest benefits of therapies that target downstream effects such as excitotoxicity or oxidative stress with the more durable impact of upstream interventions like Tofersen, emphasizing the critical importance of treating the root molecular causes rather than late-stage consequences.
Emerging Data Supporting Nuclear Pore Dysfunction in ALS
He then highlighted growing evidence that nuclear pore complex disruption may represent one of these upstream events. His team’s recent work shows that CHMP7 accumulation in the nucleus can initiate nuclear pore damage and drive the mislocalization of TDP-43, a defining hallmark of ALS. Using iPSC-derived neurons (iPSNs) as “patient biopsies,” the group is tracing how these early defects cascade into widespread gene-expression disruption.
Multiple independent data streams now support the nuclear pore as a key pathogenic node:
- Genetic Evidence:
A Project MinE transcriptome-wide study identified NUP50 as a high-probability ALS risk gene, with reduced expression in ALS brain tissue. - AI-Based Structural Predictions:
AlphaFold analyses suggest several NUP gene variants may cause structural and functional disruption of the nuclear pore. - Patient-Derived Models:
iPSNs from patients with NUP variants reveal specific NUP genes upstream of TDP-43 nuclear depletion, directly linking nuclear pore defects to ALS’s signature pathology.
Multi-Omic Data Uncover Additional TDP-43–Linked Pathways
Advances in whole-genome sequencing, transcriptomics, and single-cell RNA profiling are identifying new pathways connected to TDP-43 dysfunction. Dr. Rothstein highlighted:
- SCFD1, an ALS risk gene involved in ER–Golgi vesicle transport and synaptic signaling, with altered expression in ALS postmortem tissue.
- Norrin, which contributes to dendritic spine maintenance through astrocytic pathways, further underscoring the role of non-neuronal mechanisms in ALS vulnerability.
Together, these findings reinforce a rapidly evolving model in which upstream disruptions—particularly at the nuclear pore—trigger TDP-43 pathology and downstream neurodegeneration, guiding the search for next-generation ALS therapies.
Biomarkers Accelerate, but Challenges Remain
Rothstein emphasized the growing importance of proteomics and molecular biomarkers for early detection and disease stratification. Tools such as the NeuroMine portal from Answer ALS and collaborations with global proteomics consortia are helping map ALS biology at unprecedented resolution.
He highlighted a recent NIH study identifying a plasma protein panel with potential diagnostic utility—findings that were echoed by a European team. However, he cautioned that its real-world performance remains uncertain, as these biomarkers distinguish ALS from healthy controls and broad neurological conditions, but not necessarily from ALS mimics, which are critical for clinical decision-making.
Another emerging biomarker class—discussed further by Dr. Seddighi—is cryptic exon–containing transcripts, generated when TDP-43 loses its normal splicing function. Detectable in CSF and tissue, these markers offer a direct readout of TDP-43 dysfunction, complementing neurofilament light (NfL), which reflects neuronal injury rather than molecular mechanism.
AI and Big Data: The Next Wave of ALS Discovery
Dr. Rothstein closed by highlighting the enormous potential of AI and machine learning to model ALS heterogeneity and refine therapeutic strategies. Initiatives such as the Longitude Prize on ALS (2025–2031), the EndALS Challenge, and Project Mosaic aim to harness computational power and large-scale datasets to unravel ALS complexity and accelerate target discovery.
Scientific Highlights: New Tools for Understanding Sporadic ALS
Following the scientific presentations from Drs Miller and Rothstein, the symposium featured focused talks highlighting the latest advances in understanding ALS genetics, molecular mechanisms, and disease heterogeneity in ALS:
- Is All ALS Genetic? – Ammar Al-Chalabi, PhD
- Sporadic ALS iPSNs and Disease Heterogeneity – Alyssa Coyne, PhD
- The Genetic Landscape of Nucleoporin Variants – Julia Kaye, PhD
- Cryptically Spliced Proteins from TDP-43 Loss – Sahba Seddighi, MD-PhD Candidate
The Future of Gene Therapies: What’s Next for ALS Treatment
Written by: Dr. Jinsy Andrews (NYU Langone Health)
The Hot Topic Session: Gene Therapies, Now and in the Future opened with an energizing overview from Dr. Crooke, who highlighted the rapidly accelerating frontier of gene-specific antisense oligonucleotide (ASO) therapy. Once considered experimental and highly individualized, ASO development is now moving at unprecedented speed. Jacifusen—which originated as an N-of-1 expanded access program (EAP) for a patient with FUS-ALS—has advanced all the way to a phase 3 clinical trial, underscoring how far the field has progressed since the early landmark therapy Spinraza for spinal muscular atrophy.
ASOs are increasingly being custom-designed to target specific genetic forms of ALS, with platforms that appear readily scalable. More than 30 patients have now been treated through the n-Lorem Foundation, and among individuals with CHCHD10 mutations, 6 of 9 showed stabilization on the ALSFRS-R—a striking signal for a devastating disease. Multiple groups worldwide are pushing these technologies forward, though investigators emphasized the persistent challenge of balancing safety with the urgent need for meaningful treatments.
Next, Dr. Brown spotlighted the rise of small interfering RNA (siRNA) technologies—another precision-based strategy with parallels to ASOs, yet distinct in mechanism. Unlike ASOs, siRNAs act in the cytoplasm and consist of double-stranded RNA. SiRNA therapy is already standard of care in hereditary TTR amyloidosis, proving its clinical viability. The ALS pipeline is expanding quickly, with more than 20 preclinical and five in-human siRNA programs now moving forward. Researchers are also exploring innovative delivery approaches, including lipid nanoparticles (LNPs) and intravenous (IV) administration, to increase accessibility and tissue targeting.
Closing the session, Dr. Ahrens-Nicklas delivered an exciting look at platform gene-editing therapies. She emphasized the long-standing bottleneck in gene therapy development and the pressing need for accelerated—but safe—testing pathways for individuals with rapidly progressing diseases. Her team’s work shows what may be possible: a single IV dose of lipid nanoparticle (LNP)-delivered guide and editing RNAs dramatically altered disease progression in mouse models of phenylketonuria (PKU). Remarkably, this technology was then translated into escalating-dose treatment for a child with PKU after just a six-month development timeline—a powerful demonstration that personalized base-editing therapies can be developed and deployed rapidly when resources allow. She underscored the need for shared platforms and infrastructure to enable faster, safer gene-therapy development for all patients in need.
Overall, this Hot Topic Session underscored extraordinary progress in gene-targeted therapies for ALS. While these advances are poised to benefit individuals with known genetic forms of ALS first, the expanding understanding of gene–environment interactions suggests that these technologies may eventually help transform care for people with sporadic ALS as well
Harnessing Genetics to Understand and Treat ALS
Written by: Dr. Mark Garret (Dartmouth Hitchcock Medical Center)
Dr. Claire Clelland (University of California San Francisco) led off this exciting, cutting edge session by providing updates on the development of CRISPR-based gene therapies for C9orf72 ALS and FTD. CRISPR is a gene-editing technology with great potential to treat a wide array of genetic disorders. The first CRISPR therapy was recently approved by the FDA in 2024 for sickle cell anemia. Dr. Clelland shared her team’s exciting efforts to use CRISPR to excise the disease-causing DNA repeat expansion in C9orf72 which showed minimal off-target effects and a reduction in dipeptide repeat proteins produced from the expansion. Dr. Clelland noted that treating neurologic diseases such as ALS poses unique challenges in delivering the gene therapy to the central nervous system. She described multiple potential delivery vehicles for CRISPR therapies including adenovirus vectors, lipid nanoparticles, viral-like proteins, and ribonucleotides. To help overcome this critical challenge, Dr. Clelland described her team’s novel approach to develop a platform to optimize delivery vehicles in human tissue utilizing human cadaveric tissue which is maintained after brain death.
Dr. John Landers (UMass Chan Medical School) concluded the session with a discussion of mutant specific knockdown approaches to treat genetic forms of ALS. While decreasing expression of a disease-causing protein is often desirable, in cases where a gene has a critical function, broadly decreasing expression of that gene may exacerbate damage. Dr. Landers described his team’s approach to identify common insertions and deletions within non-coding DNA sequences and target these sequences with an ASO to specifically knock down the expression of only the mRNA containing a disease-causing change. He presented exciting data in TARDBPALS models demonstrating that this ASO treatment could reduce mutant TARDBP mRNA while preserving expression of overall TDP43 protein levels and rescuing abnormal gene expression in genes regulated by TDP43. His team is applying similar techniques to ALS caused by mutations in C9orf72 and KIF5A. He concluded that this mutant specific knockdown approach may represent a flexible strategy that could be applied to many dominantly inherited forms of ALS and other neurologic disorders.
Breakthrough Science and Recognition: Highlights from the Platform Presentations and Awards
Written by: Beverly Smits (NEALS)
This year’s Platform Presentations showcased the innovation and depth of research across the Network of Excellence for ALS. Dr. Katharina Meijboom (UMass Chan Medical School) opened with promising work on AAV-mediated gene augmentation therapy for NEK1-ALS, followed by Dr. Timothy Miller, who presented long-term findings from the Phase 3 VALOR trial and open-label extension evaluating Tofersen in SOD1-ALS. Dr. Hande Özdinler (Northwestern University) introduced a new TAR4/4 mouse model capturing upper motor neuron degeneration and neuroinflammation, while Dr. James Berry shared encouraging safety results from a study of autologous hybrid TREG/Th2 T stem cell therapy in advanced-stage ALS. The session also featured Dr. Alex Huang (Amydis), who described a fluorescent retinal tracer capable of detecting TDP-43 pathology, and Dr. Merit Cudkowicz, who presented Phase 2b PARADIGM trial results showing safety, biomarker engagement, and clinical signals supporting advancement to Phase 3.
In recognition of exceptional contributions to ALS research, Dr. Terry Heiman-Patterson presented the NEALS Abstract Awards in both Basic Science and Clinical Investigation. The Basic Science Award was presented to Dr. Federica Pilotto (University of Bern) and colleagues for their study “Talineuren (TLN): A GM1-Loaded Nanoliposomal Therapeutic Targeting Mitochondrial Dysfunction and Proteostasis in ALS.” The Clinical Investigation Award recognized Dr. Eleanor Thomas (Emory University) and collaborators for “Neurofilament Light Chain Reflects Clinical and Genetic Heterogeneity in a Real-World ALS Cohort.”
The UMN Achievement Awards, supported and presented by the Spastic Paraplegia Foundation (SPF), honored Dr. Hande Özdinler (Northwestern University) for “NU-9, in Combination with Other FDA-Approved Drugs, Have Better Outcomes in Models of TDP-43 Pathology,” and Dr. Grace Jang (Columbia University) for “Startle Reflex in Primary Lateral Sclerosis (PLS): A Comparison with Amyotrophic Lateral Sclerosis (ALS).”
Two additional awards were presented by the Sean M. Healey & AMG Center for ALS at Mass General: the Gupta Family Endowed Prize for Innovation in ALS Care, awarded to the ALS Residence Initiative for developing the first fully accessible, tech-enabled ALS residence model; and the Drs. Ayeez and Shelena Lalji & Family Student Scholar Award, presented to Cedric Günter (né Böger) (German Center for Neurodegenerative Diseases (DZNE)) for “Targeting Microtubule Retrograde Flow to Drive Axon Regeneration in ALS.”
Together, these presentations and awards reflected the creativity, rigor, and collaboration driving ALS research forward within the NEALS community.
