When two of the world's leading ALS researchers meet for the first time on a podcast, something remarkable happens. Dr. Merit Cudkowicz -Tim's close friend and arguably the world's foremost ALS expert, returns to Nothing Left Unsaid for her third appearance, this time joined by Dr. Tanya Daigle from the Allen Institute, who's pioneering genetic tools that could transform how we treat neurodegenerative diseases. Together, they reveal a future for ALS research that's closer than most people realize.

This isn't your typical medical conversation. Merit and Tanya speak with unguarded hope about gene therapies that have stopped disease progression in 40% of patients, AI-driven drug discovery that's accelerating at unprecedented rates, and precision targeting tools that could deliver treatments directly to dying motor neurons without invasive brain surgery. They discuss the real bottlenecks between laboratory breakthroughs and patient impact, why most ALS drug trials aren't actually failures, and how the field has evolved from a handful of researchers to a global collaborative effort spanning continents.

What makes this episode extraordinary is the vulnerability and honesty both scientists bring to the table. Merit shares why she rejects the phrase "treatment failure" and how the revolutionary Healey ALS Platform Trial has cut drug testing time in half. Tanya reveals how the Allen Institute accidentally stumbled into ALS research after two decades of mapping the human brain, and why that detour might be the key to unlocking targeted therapies for millions. They candidly address misconceptions that slow progress, explain why treating ALS earlier could be transformative, and offer patients and families a message of genuine, evidence-based hope.

For anyone navigating ALS, whether you're a patient, caregiver, clinician, or simply someone who wants to understand where the science actually stands, this conversation cuts through the medical jargon to deliver practical wisdom and unspoken truths about what's possible when brilliant minds collaborate fearlessly.

CHAPTERS:

00:00 Trailer 01:09 Intro 02:55 Current State of ALS Research 05:19 Misconceptions About ALS 09:32 Progress and Future of ALS Treatments 21:17 Innovations in Genetic Tools for ALS 31:59 A New Frontier in ALS Research 35:03 Efficiency of Platform Trials in ALS Research 36:59 The Importance of Funding and Science Collaboration 37:55 Advancements in Treating ALS Smarter 38:52 The Role of Biomarkers and Individualized Therapies 41:31 Dream Trials and Future Prospects 48:01 The Impact of AI in ALS Research 54:08 The Next Big Pivot in ALS Research 58:18 Hope and Collaboration in ALS Research 01:01:04 How to Be Part of ALS Community

TOPICS DISCUSSED

• ALS gene therapy breakthrough with 40% reversal rates

• Precision targeting of motor neurons using viral vectors

• The Healey Platform Trial's revolutionary approach to drug testing

• Allen Institute's cell-type mapping and its application to ALS

• IV-delivered therapies that eliminate invasive brain surgery

• AI and machine learning in drug discovery

• TDP-43 protein aggregation across 98% of ALS cases

• Why earlier treatment intervention could be game-changing

• The collaboration between lab scientists and clinical researchers

• Stem cell therapies and nanoparticle delivery systems

• Global consortiums driving unprecedented scientific collaboration

• How patients can participate in research and trials today

ABOUT THE GUESTS

Dr. Merit Cudkowicz is Chief of Neurology at Massachusetts General Hospital, Director of the Healey & AMG Center for ALS, and Professor of Neurology at Harvard Medical School. She leads the Healey ALS Platform Trial, which has revolutionized how ALS drugs are tested by cutting development time and costs in half while testing multiple therapies simultaneously. Merit has dedicated her career to transforming ALS from an untreatable diagnosis into a disease with real therapeutic options. She's Tim's close friend and most frequent guest on Nothing Left Unsaid.

Dr. Tanya Daigle is a Senior Scientist at the Allen Institute for Brain Science, where she leads genetic tool development for neuroscience research. After spending two decades mapping cell types in the healthy brain, Tanya's team is now pioneering precision gene therapy tools that can target specific motor neurons in ALS without affecting other tissues. Her work represents a new frontier in treating neurodegenerative diseases at the cellular level with unprecedented specificity.

RESOURCES & LINKS:

• Allen Institute: https://alleninstitute.org

• Healey & AMG Center for ALS at Mass General: https://www.massgeneral.org/neurology/als