The Target ALS Scientific Programs team joined global leaders in research and innovation at the International Symposium on ALS/MND in Montreal, Canada from 6-8 December, showcasing the transformative power of collaboration. Thousands of researchers from across the world came together to share new therapeutic approaches, biomarker breakthroughs, and biological discoveries of ALS and motor neurone disease (MND).

Below are some key insights from the conference, including how Target ALS serves as a touch point on many of these innovative and promising collaborations:
C9orf72 Insights:
The “Late Breaking News” presentation by Chris Pearson, a Genetics and Genome Senior Scientist and Professor at The University of Toronto, unveiled four new mechanisms of toxicity linked to C9orf72 hexanucleotide repeat expansions—shedding new light on inheritance patterns, penetrance, and pathology. These findings may explain why prior treatments targeting the C9 sense strand were not effective in patients. His research, titled “C9orf72 expansion creates the unstable folate-sensitive fragile site FRA9A” proposes that the repeat expansion leads to the formation of a fragile site on chromosome 9 called FRA9A, which can break easily when folate levels are low.
TDP43 (TAR DNA-binding protein 43) Biology Breakthroughs:
Research by Target ALS grantee and Clinical Professor and Consultant Pathologist at The University of Aberdeen, Jenna Gregory, revealed that TDP43 accumulates in peripheral tissues before symptom onset, highlighting its potential as a diagnostic biomarker. In addition, cryo-EM (cryo-electron microscopy) research spearheaded by Diana Arseni, Ph.D., Group Leader in the Neurobiology Division of the MRC Laboratory of Molecular Biology at Cambridge, uncovered heteromeric fibrillization of TDP43 with proteins like annexin A11, revealing novel mechanisms by which TDP43 can accumulate in the cytoplasm. Novel insights into the potential protective effect of TDP43 SUMOylation (Small Ubiquitin-like Modifier conjugation) from Maxime Rousseaux’s lab at the University of Ottawa also opens a new door for therapeutic intervention.include Jenna Gregory’s research, titled, “Pre-symptomatic pathological TDP-43 aggregation is a common feature in peripheral, non-central nervous system tissues in people with ALS”, could play an important role in determining if peripheral tissues might serve as a potential source for early disease detection through biopsies.
Target ALS continues to support cutting-edge TDP43 research, driving innovation in early diagnosis and therapeutic strategies via n-Lorem Foundation and Columbia University and its Silence ALS platform, aimed at discovering and developing antisense therapeutics for patients with ultra-rare forms of ALS, including TDP43 mutations. Dr. Neil Shneider, Claire Tow Associate Professor of Motor Neuron Disorders, announced at the Symposium that he recently began dosing with the Target ALS funded TDP43 ASO. Other n-Lorem ASOs, including those for patients with FUS and CHCHD10 mutations, have shown promise in data presented at this meeting and others, suggesting that treatment for patients with ultra-rare genetic ALS is possible.
Therapeutic Innovations:
The ASO (Antisense Oligonucleotide) Therapeutics session by Dr. Frank Bennett featured updates from Target ALS-funded projects targeting TDP43 and CCDC146 (Coiled-Coil Domain Containing Protein 146) mutations. The session, entitled “Antisense and siRNA-based therapeutic strategies” showed that Target ALS has been or is involved in five out of seven targets currently in the worldwide ALS therapeutic pipeline. With funding for six preclinical ASO therapeutic projects and ongoing support for next-generation approaches, Target ALS is aggressively advancing therapeutic development to address the urgent needs of people with ALS. It is also important to note that there are other disiRNA and ASO therapeutics in development beyond this list, which was presented in this session at the symposium, some of which Target ALS is also supporting.

Target ALS Take – Dr. Ellen Guss, Scientific Programs Coordinator

“Frank Bennett provided a fantastic overview that outlined the successes and current challenges of developing ASO therapeutics for ALS. Tobias Moll shared the exciting in vivo work from Johnathan Cooper-Knock’s group, showing that a CCDC146 ASO can significantly extend lifespan in an aggressive TDP-43 mouse model. This is very promising, and I’m excited that Target ALS is supporting this candidate therapeutic that preliminarily shows promise for sporadic ALS patients, a patient group where there are currently no effective therapeutic options.
In this section of the meeting, we also heard from Jonathan Glass, who is part of the Target ALS Independent Review Committee. He discussed research being conducted in collaboration with Nicholas Seyfried, highlighting why the sense strand ASOs from Biogen and Wave Therapeutics may have been unsuccessful for C9orf72 ALS patients. Nicholas is also a new Target ALS grantee in the Biomarkers Consortia. This work provided evidence that sense strand-generated DPRs may not track with disease progression, a message echoed in several posters at the ALS/MND Symposium. Better understanding of the biology explaining the lack of efficacy in these trials will help guide the antisense strand therapeutic projects that Target ALS is currently funding. All in all, this session included excellent research and biology, a dissection of past challenges, and hope for the future. It is exciting that Target ALS is deeply involved in work in this space, and our open New Modalities for ALS therapeutics in DNA/RNA RFA aims to include even more work in the gene therapy space in our portfolio.”
Clinical Trial Updates:
Stephanie Fradette, Vice President and head of the Neuromuscular Development Unit at Biogen, shared progress from Biogen’s ATLAS (ALS Targeting the Lowering of SOD1) trial, the first clinical trial designed to prevent ALS in SOD1 (Superoxide Dismutase 1) mutation carriers by monitoring NfL (Neurofilament Light chain) levels to optimize treatment timing. Target ALS is preparing to release longitudinal NfL data from our Natural History Study early next year, contributing critical data to inform this type of clinical trial design. The session, titled “Design of preventative trials in ALS”, also highlighted the opportunity for those interested to participate in the ATLAS clinical trial.
Target ALS Take – Dr. Amy Easton, Senior Director of Scientific Programs

“As Michael Benatar described in the Friday morning session, disease processes can start years before patients experience their first clinical signs of ALS. Through the ATLAS study and large, collaborative Natural History Studies, we are getting closer to identifying biomarkers that predict progression during the prodromal and early stages of disease, allowing physicians to intervene early to prevent loss of motor function and prolong life.
Early intervention is feasible when the genetic or biological cause of the disease, in this case the mutant SOD1 gene, is known for that patient. I applaud Biogen for launching this ambitious trial and expect that learnings from the trial will be applicable, not just SOD1 mutation carriers, but to other genetic forms of ALS. Target ALS is helping to break down barriers to early intervention through our research studies tracking disease progression over time and through the research we fund, focused on discovering the genetic causes of disease.”
The importance of diversity in research
Many of the presentations at the International Symposium on ALS/MND shared work surrounding selective vulnerability, neuron heterogeneity, glial contributions, and ALS/FTD. Multiple groups presented evidence that glia contribute to motor neuron death, and work conducted at the University of Sheffield in Professor Dame Pamela J. Shaw’s group indicated that astrocytes from C9-ALS patients are deleterious to both motor and cortical neurons, while astrocytes from C9-FTD patients are selectively damaging to cortical neurons. Further understanding the biology at play could help uncover new therapeutics for ALS and FTD. This is a priority for Target ALS, which funds the exploration of glia in disease through its Basic Biology 2024 grant as well as selective vulnerability through Springboard Fellow Aude Chiot’s research. Target ALS also supports work to better understand diseases related to ALS, including FTD. Researchers seeking to understand either disease can request relevant human tissue from our Postmortem Tissue Core or access and analyze spatial transcriptomics data from postmortem ALS and FTD tissue in the Target ALS Data Engine.
Preliminary work presented at the conference that looks at the genetics of sub-saharan African populations with ALS suggests that numerous risk alleles are present in African populations, including C9orf72 repeat expansion and SOD1. Data like this is critical to inform the worldwide ALS research community which genes may be included in genetic screening for early detection of ALS and may also be targeted by therapeutics to benefit patients of all ancestral backgrounds.
Target ALS’s Global Natural History & Longitudinal Biofluids Study Historically, ALS research has primarily included individuals of European descent, which limits our understanding of the disease across different races and ethnicities. Our Global Natural History Study aims to enhance diversity by enrolling a broader participant cohort, targeting at least 800 symptomatic ALS participants and 200 healthy controls from various backgrounds. This is crucial for identifying genetic risk factors and developing effective treatments that work for everyone. |

Diagnostic Updates:
According to research presented by Dr. Patrick Weydt in Germany, combining serum neurofilament light (NfL) with serum cardiac troponin T (cTnT) can significantly enhance the diagnostic accuracy for ALS, as elevated levels of both biomarkers are observed in ALS patients, providing a more comprehensive picture of neurodegenerative damage and potentially improving disease monitoring. Currently, no definitive biomarker exists for ALS, making early diagnosis and monitoring of disease progression challenging. Biofluids, such as blood, cerebrospinal fluid, and saliva, are critical because they can provide non-invasive, accessible samples that may contain key biomarkers, enabling earlier detection, more accurate diagnosis, and better tracking of therapeutic responses.
Target ALS Take – Laura Dugom, Clinical Research Scientist
“I really enjoyed the session focused on biomarkers because it highlighted the potential of cardiac troponin T as a serum marker for muscle damage and disease progression in ALS. Unlike serum neurofilament levels, serum cardiac troponin T correlated with the respiratory domain of the revised ALS Functional Rating Scale and pulmonary function parameters. Many of the biomarker sessions presented cross-sectional findings. This highlights the urgent need for longitudinal samples and corresponding clinical data, which are accessible through the Target ALS biofluids repository and data engine to accelerate future biomarker discovery.”
Support the Global ALS Research Community
Target ALS is involved in many innovative research projects that aim to accelerate the development of effective treatments and diagnostics for ALS. With over 16 presentations and posters acknowledging Target ALS at the Symposium, we are proud to see our work catalyzing progress.
By supporting these cutting-edge initiatives, Target ALS is playing a critical role in transforming ALS research and bringing us closer to effective therapies and better diagnostic tools. Through continued collaboration, data sharing, and innovative research, Target ALS is helping to pave the way for breakthroughs that could dramatically improve outcomes for the ALS community.Your support helps us provide essential tools to researchers around the world, ensuring that critical discoveries are within reach for all. Join us in empowering the global ALS research community and driving progress toward effective treatments. Make a difference today—every donation brings us one step closer to a world where Everyone Lives.