A new study from scientists at Northwestern University Feinberg School of Medicine sheds light on how amyotrophic lateral sclerosis (ALS) unfolds in the body. Specifically, they found that the disease proceeds through a “domino-like” sequence of events that begins with an early breakdown inside motor neurons that is followed by a damaging inflammatory response. Insights from this study could help explain why the disease worsens over time, why some patients progress faster than others, and how future treatments could be more personalized. Details of the work are available in a new Nature Neuroscience paper titled “Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming.” On average, patients with ALS live three years after symptoms begin, although some can survive closer to 10 years. Exactly what drives these differences in survival is unclear. “This study reveals that ALS is not a single event but a domino-like cascade that begins inside motor neurons with TDP-43 pathology and is then amplified by a damaging immune response in the bloodstream and spinal cord,” said David Gate, PhD, director of the Abrams Research Center on Neurogenomics at Feinberg and co-corresponding author on the study. Specifically, the study found that immune cells converge at sites of motor neuron loss and TDP-43 pathology with distinct inflammatory patterns depending on the type of ALS and how quickly the disease progresses. As Evangelos Kiskinis, PhD, an associate professor of neurology and neuroscience at Feinberg and a co-corresponding author on the study, explained it, “the…
