Anle138b is an oligomeric aggregation inhibitor which can block the formation of pathological aggregates of prion protein (PrP(Sc)) and of α-synuclein (α-syn) deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).
Anle138b ,the novel oligomer modulator, is an inhibitor of α-synuclein (α-syn) and prion-protein (PrPSc) aggregation that reduces the progression of prion and Parkinson′s disease in animal models. In vitro, anle138b blocked the formation of pathological aggregates of PrPSc and α-syn, which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). In mouse models of prion disease and PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. [1] Anle138b is capable of prolonging the survival of prion-infected mice even after onset of symptoms, and anle138b started in the symptomatic disease phase at 50 weeks of life has a significant effect on survival until onset of terminal disease[2].Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers[1]. Anle138b strongly inhibited all prion strains including BSE-derived and human prions in a purely human system and had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood–brain-barrier penetration , which indicated that this compound may also be useful for treatment of human prion disease[1].
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