Progress in ALS research doesn’t happen in isolation. It happens when scientists gather, challenge assumptions, share data, and test new ideas against the realities of the disease. This month, members of the Target ALS science team participated in two major international meetings shaping the future of ALS research: the International ALS/MND Symposium in San Diego and the International Alliance of ALS/MND Associations Meeting in Toronto.
Across both meetings, one message was clear: there remains a high unmet need for new therapies to treat ALS. Target ALS is paving the way for the next wave of biomarkers and targets through funding innovative projects, providing human samples, tools and data to bolster translational programs, and collaborating with communities to fight ALS on a global scale through AGRI – our ALS Global Research Initiative.
San Diego: Where the Science Is Heading
At the International Symposium on ALS/MND in San Diego, Amy Easton, PhD, Michael Marks, PhD, and Daniel Weatherill, PhD joined hundreds of researchers from around the world to review the latest advances across basic biology, biomarkers, and therapeutics.
Key areas of interest highlighted throughout the 3-day conference included: development and improvement of stem-cell-based models of disease and state-of-the-art methods for data capture and integration. Biological themes included RNA dysregulation, altered proteostasis, role of non-neuronal cell types in disease, and genetics. In addition, a number of groups presented updates on clinical trials, where Natural History Studies were a highlight. A number of scientists presented new biomarker findings, proposing novel frameworks for disease stage or disease region. Across hundreds of presentations and posters, the team saw broad confirmation that Target ALS is investing in the key scientific areas of interest. Of note, key themes and presentations from the meeting included:
A growing momentum continues to build around advancing human disease models using transdifferentiation and organoid and assembloid systems, which improves the translational accuracy of human motor neuron biology. In particular, organoids are miniature 3-dimentional structures that emulate the human brain and spinal cord, and can be developed using patient-derived induced pluripotent stem cells. Organoids can be single-cell or include a diverse collection of cell types, creating a model that more closely reflects living tissue. Jimena Andersen and Kevin Rhine presentations illustrated how these novel approaches allow researchers to study ALS in human-relevant systems, rather than relying solely on animal models, and were repeatedly highlighted as critical to improving early drug screening and translation. These innovative approaches reinforce the importance of Target ALS’s on-going expansion of our Stem Cell Core to create a well-characterized suite of patient and isogenic control lines for distribution in early 2026.
Another major theme showcased was the growing impact of AI- and machine-learning–driven analysis of multimodal datasets in revealing disease mechanisms with greater temporal resolution and precision. For example, Andrew Strange applied transformer-based predictive multiomics to identify pre-symptomatic proteomic biomarkers that forecast ALS onset with ~70% average precision and specificity relative to other neurodegenerative diseases. Zuzana Butti combined spatial and single-cell analyses of prefrontal and language cortices to show heightened reactive astrocytes and monocyte-macrophage activation, vascular-associated changes, and glial dysfunction associated with cognitive impairment in ALS. Similarly, Eran Hornstein (Weizmann) gave a beautiful presentation on MoMaps, a high content imaging platform detecting detailed pictures of cellular organelles and Sam Sances (In Sitro) presented on their drug discovery platform, which uses an AI pipeline to construct co-embeddings on multi-omic datasets, screening at genome wide scales, to create a multiplex readout using ML methods. In Sitro’s DeepCE screen, used in drug discovery efforts, integrates Pertub-Seq in combination with multiple gene knockout strategies to evaluate previously unmeasured neuronal phenotypes and create more complete phenotypic similarities with ALS-cells. High-throughput imaging combined with AI and ML approaches enables unbiased target detection and engagement, and characterization of multimodal phenotypic changes at scale. Additionally, these complementary approaches allow researchers to predict disease based on molecular and cellular phenotyping of the cells via unbiased screens.
New mechanistic underpinnings of ALS are under exploration, leading to refinements in understanding the pathological cascade of events leading to motor neuron death. For example, Don Cleveland’s group reports that hyperacetylation of TDP‑43 functions as an initiating step in the proteostatic cascade underlying ALS, arising with proteasome dysfunction and leading to importin‑α–dependent nuclear import failure, cytoplasmic accumulation, and aggregation, plausibly contributing to neuronal loss. Importantly, reducing TDP‑43 acetylation restores normal nuclear localization even under proteasome stress, highlighting post‑translational control of TDP‑43 as a potential therapeutic target.
Cryptic exon (CE) expression and translation was frequently highlighted in several presentations. Notably Dr. William (Bill) Seely showed that CE splicing has been linked to greater neuronal sub-type vulnerability. Dr. Jonathan Glass presented preliminary data showing that ELAVL3, a neuronal RNA-binding protein, can be manipulated to correct wide-spread CE expression downstream of TDP-43 dysfunction.
A number of biomarker presentations were sprinkled throughout the week, potentially the greatest area of advancement in ALS research. Lindenborn and team (DZNE) proposed that Troponin T and Neurofilament Light could be simultaneously assayed and serve as biomarkers for muscle degeneration and neurodegeneration respectively. Michael Benatar (U. Miami) presented biomarkers that may predict phenoconversion to clinical manifest disease using the ultrasensitive Olink HT platform. Similarly, Tzeplaeff and team (Technical University of Munich) shared biomarker data from a NULISA panel in presymptomatic and symptomatic subjects. In poster format, TMT-MS proteomics data from the Target ALS GNHS, generated in the Zetterberg lab, highlighted new and existing biomarkers of disease.
While some findings were intriguing and even exciting, the team emphasized the value of scientific rigor. The Q&A and post-meeting discussions reinforced the importance of careful validation and critical evaluation, even when data comes from highly respected laboratories. This discipline remains central to how Target ALS approaches funding and collaboration.
Toronto: Strengthening a Global Research Ecosystem
At the International Alliance of ALS/MND Associations Meeting in Toronto, Laura Dugom, Associate Director of Clinical Research, represented Target ALS alongside leaders from ALS organizations from 30 countries. This meeting brought together over 250 health care professionals, creating a space for a truly global exchange focused on advancing ALS/MND care.
The Alliance meeting emphasized how global research efforts can work together more effectively. A key takeaway from Toronto was the strong interest in Target ALS’s global research strategy, particularly the ALS Global Research Initiative (AGRI). Participants responded positively to the organization’s emphasis on geographic diversity, equitable participation, and building research infrastructure that reflects the global ALS population.
Conversations with international partners underscored a shared need for studies that are thoughtfully designed from end to end, including how data and biosamples are shared and utilized. Target ALS’s approach, which prioritizes open access and long-term usability, stood out as a model for how global collaboration can be done well.
The meeting also reinforced the importance of coordination rather than duplication. As more countries launch national and regional ALS studies, there is growing recognition that shared standards, aligned platforms, and transparent data sharing will be essential to accelerating progress worldwide.
What This Means for Target ALS
Together, these two meetings reinforced several core principles that guide Target ALS’s work:
- Rigorous, high-quality basic science paired with state-of-the-art technology fuels innovation in biomarker and therapeutic discovery.
- Open, high-quality datasets are central to discovery and translation.
- Global collaboration and inclusion are no longer optional but essential.
- Urgency matters. People living with ALS cannot afford slow, siloed progress.
For Target ALS, these conversations confirmed that our model of funding, enabling, and conducting research is not only timely but increasingly necessary. As the ALS research landscape evolves, Target ALS will remain agile, directing resources to develop promising avenues of treatment and biomarker discovery
