Panel Discussion: How Can We Treat Underlying TDP43 Pathology Outside of Clinical Presentation to Develop Effective Treatments in ALS, FTD & Beyond?

• What is the current understanding of TDP‑43 pathology across ALS, FTD, and related neurodegenerative diseases, and how does it inform therapeutic strategies?
• How can therapies be designed to target upstream TDP‑43 mislocalization, aggregation, or loss-of-function, independent of clinical symptom presentation?
• The role of biomarkers and imaging in detecting subclinical TDP‑43 pathology and enabling earlier intervention in patients
• Challenges and opportunities in translating preclinical findings into human studies, including target engagement, dosing strategies, and safety considerations
• Potential combinatorial approaches, such as pairing TDP‑43-targeted therapies with neuroprotective or gene-modulating modalities to enhance efficacy

Speakers:

Irina Antonijevic

Chief Medical Officer

Trace Neuroscience

Kelly Glajch

Scientific Director, Rare Neurology- Neuroscience Therapeutic Area Unit

Takeda

Joseph Klim

Director of Neuroscience

NuCyRNA Therapeutics

John Replogle

Postdoctoral Fellow

National Institutes of Health (NIH)