3 minute read
Looking MS in the Eye
Among the 25+ laboratories conducting basic science research at Kellogg, it might seem surprising to find one focused on neurodegenerative diseases like Multiple Sclerosis (MS). But that’s just one of the unexpected things about the Werneburg lab.
Neurobiologist Sebastian Werneburg, Ph.D., joined the University of Michigan in 2022 as a faculty member in the Departments of Ophthalmology & Visual Sciences and Molecular & Integrative Physiology, and as an affiliate of the Michigan Neuroscience Institute. His laboratory studies how disruptions of synapses in the brain and retina, the connections between nerve cells that allow networks of neurons to communicate and facilitate proper brain function, contribute to disease progression and severity in neurodegenerative conditions like MS.
Despite decades of research into MS, degeneration of neurons and the breakdown of connections between those neurons (neural circuits) continue to cause permanent disability, representing an urgent unmet clinical need. MS is characterized by pronounced inflammation, the destruction of myelin (the protective sheath around nerves), and damage to nerve fibers. Current therapies primarily focus on the immune system’s attacks on these central nervous system components. However, they fall short in addressing the deterioration, or degeneration, of neural circuits that lead to the disabling consequences of MS.
Dr. Werneburg’s team uses the visual system, a neural circuit frequently affected in MS, to unravel these complexities. They discovered that microglia, the brain's immune cells, cause a loss of connections, or synapses, between nerve cells in the visual system by eating synaptic connections. They further describe that synapse loss, which causes the entire system to dysfunction, can occur even before the loss of neural fibers and myelin damage. While this work highlights the role of synapse disruption in MS-related dysfunctions, much about how these synaptic circuits break down remains unclear.
Dr. Werneburg explains, “Synaptic circuitry is a vastly understudied aspect of MS, in part because it is not as easily noticeable as other factors. But our work highlights that disruptions in synapses, including the visual system, are very likely key drivers of disease progression and severity in MS.”
“One reason to suspect this is that similar disturbances in brain circuitry are the strongest link to cognitive impairment in another neurodegenerative disorder, Alzheimer’s disease,” he adds.
To test this novel theory, the Werneburg lab aims to investigate key biological processes such as alterations in neuronal activity and microglial reactivity to better understand how the nervous and immune systems interact to drive neural circuit disruption. Another project focuses on the potential to repair synaptic circuits damaged in MS. “Most patients are first diagnosed with the relapsing/remitting form of MS, which alternates between phases of degeneration (relapse) and regeneration (remission),” he explains. “That potential for regeneration—however tenuous it may be—may represent another key target for therapeutic interventions by enhancing synaptic repair.”
His team also conducts research specific to retinal dysfunction in MS, recently identifying degeneration of synapses in the retina as a potential diagnostic target to predict and track the progression of MS.
These innovative research directions have significant clinical relevance. Establishing a clear link between synaptic circuitry disruptions and neural degeneration could pave the way for groundbreaking treatments to halt or even reverse functional decline seen in MS and other related neurodegenerative diseases. Thus, Dr. Werneburg’s novel research focus holds the promise of filling critical gaps in our understanding and treatment of these debilitating conditions.
