The new drug circumvents the neurotoxic inflammatory side effects that occur with conventional treatments. Aduhelm, a monoclonal antibody that targets amyloid beta (A), recently became the first United States Food and Drug Administration (FDA)-approved drug for Alzheimer’s disease (AD) based on i
The researchers believe that their approach might be a breakthrough in treating Alzheimer’s disease without triggering inflammatory side effects or synapse loss.
Furthermore, approximately 40% of patients treated with this antibody experienced serious side effects such as cerebral edemas and hemorrhages , which are likely related to inflammatory responses in the brain caused by the Aβ antibody binding Fc receptors of immune cells such as microglia and macrophages.
in South Korea created Aβ-Gas6, a new fusion protein drug that successfully eliminates Aβ through a completely different mechanism than Aβ antibody-based immunotherapy. In a mouse model of Alzheimer’s disease, A-Gas6 not only eliminated Aβ more effectively, but it also avoided the neurotoxic inflammatory side effects associated with conventional antibody treatments.
The professors and their team demonstrated that the resulting αAβ-Gas6 induced Aβ engulfment by activating not only microglial but also astrocytic phagocytosis since TAM phagocytic receptors are highly expressed by these two major phagocytes in the brain. Importantly, αAβ-Gas6 promoted the robust uptake of Aβ without showing any signs of inflammation and neurotoxicity, which contrasts sharply with the treatment using an Aβ monoclonal antibody.
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