Les Turner ALS Center at Northwestern Medicine

Keynote Presentation: Antisense based therapy for rare neurological diseases

Currently there are multiple genetic based medicines being pursued for rare neurological diseases including antisense technology, gene therapy and gene editing technologies. Antisense oligonucleotides (ASOs are one of the more advanced technologies. ASOs are synthetic, chemical modified nucleic acid analogs designed to bind to RNA by Watson-Crick base paring. Upon binding to the RNA, ASOs modulate the function of the targeted RNA through a variety of mechanisms. Both protein coding, as well as non-coding RNAs, can be targets of ASO based drugs, significantly broadening therapeutic targets for drug discovery compared to small molecules and protein based therapeutics. The approval of nusinersen (Spinraza™) as a treatment for spinal muscular atrophy (SMA) and the recent approval of tofersen (Qalsody) for familial ALS validates the utility of antisense drugs for the treatment of motor neuron diseases. The application of antisense technology as potential therapy for other rare neurodegenerative diseases and neurodevelopmental disorders will be discussed.

About the Keynote Speaker: C. Frank Bennett, PhD

Dr. Bennett is the executive vice president and chief scientific officer at Ionis Pharmaceuticals and one of the founding members of the company. He is responsible for continuing to advance Ionis’ technology and expanding the company’s drug discovery platform. Dr. Bennett is also the franchise leader for gene-editing programs at Ionis. He has been involved in the development of antisense oligonucleotides as therapeutic agents, including research on the application of oligonucleotides for inflammatory, neurodegenerative diseases and cancer, oligonucleotide delivery, pharmacokinetics and medicinal chemistry. Dr. Bennett lead the discovery and development of nusinersen and the discovery of tofersen and tominersen.

Research Presentations:

Untangling the convergence of disease mechanisms in ALS using personalized iPSC technologies

Evangelos Kiskinis, PhD, is an associate professor of neurology and neuroscience at Northwestern University Feinberg School of Medicine and a New York Stem Cell Foundation Robertson Investigator. Kiskinis earned a PhD from Imperial College London and carried out postdoctoral training at Harvard University, where he pioneered the first models of ALS using personalized stem cell-based approaches. In 2015, his laboratory was established at the Les Turner ALS Center at Northwestern. The Kiskinis Lab seeks to harness the power of pluripotent stem cells to understand how neuronal function is impaired in ALS/FTD patients as well as identify points of targeted and effective therapeutic intervention for ALS/FTD. Kiskinis also serves as the scientific director of the Stem Cell Core Facility at Northwestern. 

Talk Description:  In this talk, Dr. Kiskinis will describe findings from investigating distinct genetic causes of ALS using iPSC models as well as novel mechanistic interaction between TDP43 dysfunction and neuronal excitability that is relevant for sporadic ALS disease. 

How neuronal stress and brain trauma may contribute to ALS pathogenesis

Daryl A. Bosco, PhD, is a professor of Neurology at UMass Chan Medical School. Dr. Bosco’s scientific career began with a PhD in bio-organic chemistry from Brandeis University in Massachusetts and a post-doctoral fellowship at the Scripps Research Institute in California, where she studied protein structure and misfolding in the context of neurodegeneration. Dr. Bosco was then an Instructor at Harvard Medical School in Massachusetts, where she began working on ALS. In 2008, Dr. Bosco established her independent research laboratory at UMass Chan Medical School. The Bosco Lab is ​​investigating the mechanisms underlying ALS and related disorders such as frontotemporal dementia.  

Talk Description: The Bosco Lab is studying stress as an upstream trigger of neuron death in ALS. These studies are based on observations that neurons in ALS patients become overactivated because of both altered neuronal connections and metabolite imbalances within the central nervous system. Dr. Bosco will present recent research showing that ALS neurons are more susceptible to external stressors such as brain trauma.   

Potential role of cardiolipin nanoparticles in improving upper motor neuron health in amyotrophic lateral sclerosis

Mukesh Guatam, PhD, is a research assistant professor in the Northwestern University Feinberg School of Medicine Department of Neurology. He received his MS from Barkatullah University in Bhopal, India in Bioscience with specialization in Biotechnology; and his PhD from University of Delhi, India, Department of Zoology. Dr. Gautam's research is focused on understanding underlying mechanisms that contribute to vulnerability of motor neurons in the context ALS. He is particularly interested in exosomes-mediated cellular communication, epigenetic regulation of gene expression, and identification of targets for therapy development. Dr. Gautam uses in vivo and in vitro model systems, immuno-coupled electron microscopy (iEM), correlative light electron microscopy (CLEM), extracellular vesicles, and next-generation sequencing approaches to answer his research questions. 

Talk Description: Dr. Guatam will discuss nanoparticle mediated improvement of mitochondria structure as a potential treatment strategy for ALS. 

Countering deleterious phase transitions in ALS/FTD

James  Shorter, PhD, is a professor of biochemistry and biophysics at the University of Pennsylvania. He received his MA in Biology from the University of Oxford and a PhD in Cell Biology from University College London. His postdoctoral training was at Yale University and the Whitehead Institute for Biomedical Research at MIT. His lab focuses on mechanisms to counter deleterious phase transitions in neurodegenerative disease. 

Talk Description: Countering deleterious phase transitions in ALS/FTD. In this talk, Dr. Shorter will provide his thoughts on how to counter deleterious phase transitions in ALS/FTD. 

From axon damage to disease: common mechanisms in neurodegeneration 

Claire Le Pichon, PhD, is an investigator in the Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. She earned her PhD in Biological Sciences from Columbia University in 2007, then joined the Translational Neuroscience group at Genentech, where she worked on several pipeline targets for neurodegenerative disease, including the axon injury signaling kinase DLK. She started her laboratory at the NIH in 2016, where she employs a multidisciplinary approach to investigate cellular mechanisms underlying neuronal dysfunction and degeneration, using mice and iPSC-derived neurons as model systems.

Talk description: Dr. Le Pichon will present work on axon injury signaling as a common pathway in neurodegeneration, as well as current efforts to understand fundamental differences between vulnerable and resilient populations of motor neurons in ALS. 

Clinical Conversations 

Join us for an engaging discussion on the latest in ALS care and clinical research, from the perspectives of a clinician and two people living with ALS. By uniting the expertise of specialists in fields like pulmonology, nutrition, and social work, multidisciplinary care is making a difference on the quality of life and health of people living with ALS and their caregivers. The Lois Insolia ALS Clinic at the Les Turner ALS Center at Northwestern Medicine has a comprehensive multidisciplinary team and is actively involved in multi-center drug trials and other clinical research. In this panel, you'll learn how clinicians and people living with ALS are shaping the future of multidisciplinary care, research, and community support, and you’ll have an opportunity to ask questions about the latest advancements in these fields.

Senda Ajroud-Driss, MD, is a professor in the Ken & Ruth Davee Department of Neurology at the Northwestern University Feinberg School of Medicine, where she also serves as program director of the neuromuscular medicine fellowship. Dr. Driss received her medical degree from The Medical School of Tunis, Tunisia, then completed her neurology residency at the University of Illinois at Chicago and a neuromuscular fellowship at Northwestern. She is board-certified in neurology and in neuromuscular medicine and has been treating patients with ALS in the Lois Insolia Clinic at the Les Turner ALS Center for nearly 20 years. Dr. Driss also leads the Les Turner ALS Center’s clinical trial program. 

Tina Cascio, RN, BSN, joined the Les Turner ALS Foundation's Board of Directors in 2022 and serves on its Support Services Committee. Tina cared for her mom throughout her fight with ALS until her mom passed away in 2018. She is now in her own battle after having been diagnosed with ALS in 2020. Tina has been involved in community outreach and familial sponsor programs as well as the organization Her ALS Story. Tina's entire career to this point has been in the medical field and she considers herself a temporarily retired nurse. Once there is a cure for ALS, she plans on returning to care for her patients. 

Janie Gobeli serves as an advisory committee member for the HEALEY ALS Platform Trial and the QurAlis/CISCRP Global Patient Advisory Board, an ALS Research Ambassador for the Northeast ALS Consortium (NEALS), and a reviewer for the Les Turner ALS Foundation’s educational materials and programs. She was diagnosed with ALS in 2021. As a former elementary education teacher and licensed cosmetologist, she is proud to work as an ALS educator, advisor, and speaker because it allows her to be a voice for all ALS warriors and follow her lifelong passion for learning and educating others.