Revolutionising Neurodegenerative Disease Treatment: Immunotherapy and Advanced Stem Cell Techniques What drives the progression of neurodegenerative diseases like ALS, Alzheimer’s, and MS? Unraveling the mechanisms of neuroinflammation is at the heart of Prof. Bob Harris’s research at the Karolinska Institutet. His team is pioneering new therapeutic approaches by targeting microglial activity and harnessing advanced stem cell techniques. Their goal is to transform treatment strategies for these debilitating conditions. Neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), and chronic Multiple Sclerosis (MS) are marked by a common culprit: neuroinflammation. This inflammation is driven by the chronic activation of microglia, the brain’s resident immune cells, and begins as a protective mechanism. However, when prolonged, it is a cause of destructive cytotoxicity and neurodegeneration. We spoke with Prof. Bob Harris, the leader of the research group Applied Immunology and Immunotherapy at the Centre for Molecular Medicine, Karolinska Institutet. He and his research group are focused on understanding the underlying mechanisms of chronic neurodegenerative diseases and translating this knowledge into practical treatment solutions. Given that no effective treatments currently exist for neurodegenerative diseases, their objective is to develop novel therapeutic platforms to address this significant unmet medical need.
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A brain on fire Normally, microglia play a role in maintaining brain health. They release factors that promote neuronal survival and restoration of neuronal function after injury. But perpetual activation prevents them from executing their physiological and beneficial functions. Chronically activated microglia release harmful cytokines, oxygen radicals, and other molecules that impair neuronal function and threaten cell survival. Additionally, the essential phagocytic function of microglia- their ability to clear out cellular waste and misfolded proteins— is compromised in neurodegenerative diseases. This failure results in the buildup of toxic aggregates in the central nervous system (CNS), which in turn triggers further microglial activation, creating a vicious cycle of inflammation and damage. For example, in ALS, overactive microglia gather around dying motor neurons. Their numbers directly correlate with the extent of neuron damage.
Similarly, in MS, activated microglia are found at sites of demyelination, interacting with T and B cells through factors released behind a closed blood-brain barrier (BBB). Scientific evidence shows that activated microglia and monocytes can have both beneficial and detrimental effects at different disease stages. This means that approaches that modulate microglial activity can potentially be used in the treatment of a wide range of neurodegenerative diseases. “Strategies that modulate microglial activity and clearance function are thus promising for treatment of a range of neurodegenerative diseases” explains Prof. Harris.
Putting the Fire Out Before Rebuilding Immunotherapy, which involves modulating immune cells to reduce or stop inflammatory disease processes, has revolutionized the treatment of certain cancers and autoimmune diseases.
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