Northwestern physicians, scientists and people living with ALS gathered at the 12th annual Les Turner Symposium on ALS to share knowledge and celebrate advances in understanding and treating the disease.
The symposium, held on November 7, is a one-day event featuring presentations on the latest research on amyotrophic lateral sclerosis, or ALS. This year’s event was the first time the symposium has been held in-person since 2019, with a livestream option available to viewers around the world.
ALS, also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease. It affects an estimated 350,000 people worldwide and has an average survival rate of three years.
The symposium is sponsored by the Les Turner ALS Center at Northwestern Medicine, which combines ALS research, clinical expertise and educational opportunities to accelerate advances in ALS treatment. The Les Turner ALS Foundation, one of the country’s oldest independent ALS organizations, established the center.
“The progress we are seeing today in basic science research and approved therapeutics and advances in clinical care would not be possible if groups like the Les Turner ALS Foundation had not funded ALS research and clinical care for the last 40 years,” said Andrea Pauls Backman, MBA, chief executive officer of the Les Turner ALS Foundation. “ALS is an incredibly complex disease spectrum and we are uncovering potential pathways to stopping this disease, but it is not happening quickly enough. Until we have ALS cures, we will continue to support people living with ALS and their families to help them confidently navigate this disease, including offering this symposium every year.”
Robert Kalb, MD, the Joan and Paul Rubschlager Professor of Neurology, chief of Neuromuscular Disease in the Ken and Ruth Davee Department of Neurology and director of the Les Turner ALS Center, presented his research on how inherited ALS genes “re-wire” the mitochondria of cells at the onset of the disease, affecting how neurons use and store ATP, the cell’s source of energy.
This is a new potential target for treating ALS, Kalb said.
Jonathan Brent, MD, PhD, assistant professor of Neurology in the Division of Neuromuscular Disease, discussed his research into a mutated protein, KIF5A, and the mechanisms by which it disrupts cellular homeostasis in ALS.
The mutated protein causes disruptions in intracellular trafficking, Brent said, or the process by which cells move supplies from one part of the cell to another. The mutation causes KIF5A to be overactive in moving around mitochondria within the cell, Brent said, similar to a tow truck with its brakes cut.
“We think ALS blocks the protein from shutting off and traps it in this consistently active state,” Brent said. “As a result, as opposed to being recycled back to where needs to go, the protein lodges in the tips of the neurite.”
Evangelos Kiskinis, PhD, assistant professor of Neurology in the Division of Neuromuscular Disease, spoke about his investigation into a genetic driver of ALS and how the gene produces dipeptide proteins which have toxic interactions with RNA.
The keynote speaker, Nicholas Maragakis, MD, medical director of the Johns Hopkins ALS Clinical Trials Unit and director of the ALS Center for Cell Therapy and Regeneration Research and professor of Neurology, presented his lab’s work with utilizing pluripotent stem cells as a platform for understanding the mechanisms behind ALS.
Additional presenters included Cat Lutz, PhD, MBA, vice president for the Rare Disease Translational Center at Jackson Laboratory, who detailed the numerous mouse models available for ALS research.
Clotilde Lagier-Tourenne, MD, PhD, associate professor of Neurology at the Massachusetts General Hospital and Harvard Medical School, shared her work on the emerging therapeutic target for ALS, Stathmin-2.
Hande Ozdinler, PhD, associate professor of Neurology in the Division of Neuromuscular Disease, presented on her lab’s work to identify potential biomarkers for ALS in upper motor neurons.
“Currently, we don’t really have good biomarkers to distinguish patients or to reveal the timing and extent of neuronal degeneration,” Ozdinler said. “Without the proper biomarkers, it’s very hard for drug companies to delve into these big and very expensive efforts because they need a way to tell if their treatment is working.”
Erik P. Pioro, MD, PhD, vice chair of Translational Neurology and the Lewis John Pollock Professor of Neurology, presented his work on characterizing the unique patterns of brain degradation in a subset of ALS patients shown in MRI scans.
Pioro looked at the degradation of white matter in the brains of three subgroups of ALS patients: those experiencing degeneration of the corticospinal tract (CST hyperintensity), patients who were not experiencing corticospinal tract degradation, and ALS patients with frontotemporal dementia.
“We have shown with high clinical and advanced grade MRI analyses that ALS patients with and without CST hyperintensity appeared to be distinct subtypes of ALS with differing regions of brain degeneration,” Pioro said. “It also suggests these subgroups may have unique mechanisms of disease progression. That supports stratification for clinical trials and, if better understood, could lead to identifying specific molecular targets for novel therapies.”
In addition to scientific presentations and a research poster session, a panel of Northwestern physicians and Les Turner ALS Foundation staff fielded questions from patients and caregivers seeking advice on emerging treatment options and other ALS-related topics.
Panelists included Colin Franz, MD, PhD ’13, ’17 GME, assistant professor of Neurology and of Physical Medicine and Rehabilitation; Senda Ajroud-Driss, MD, associate professor in of Neurology in the Division of Neuromuscular Disease and director of the Lois Insolia ALS Clinic at the Les Turner ALS Center; John Coleman III, MD, associate professor of Medicine in the Division of Pulmonary and Critical Care and of Neurology; Lauren Webb, LCSW, director of Support Services and Education at the Les Turner ALS Foundation; and keynote speaker Maragakis.
