Unmet Need
Lewy bodies dementia (LBD) is one of the most common causes of dementia, including Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). Both clinical and experimental observations support the hypothesis of prion-like α-syn driving α-synucleinopathy, hence targeting the prion-like α-syn may be a new approach to treat LBD and related α-synucleinopathies. Currently, there is no cure for LBD.
Technology Overview
Researchers have designed the first disulfide bond-free synthetic nanobody libraries to select nanobodies that preferentially bind to the pathogenic α-syn PFF but not the α-syn monomer as a novel therapy for α-synucleinopathies. Expression of these PFF-Nanobodies by adeno-associated virus (AAV-PFFNBs) transduction was shown to decrease the pathological phosphorylation of α-syn in primary cortical neuron cultures. Intraventricular injection of AAV-PFFNBs efficiently prevented the pathogenic α-syn spreading to the cortex induced by the unilateral intrastriatal injection of α-syn PFF.
Stage of Development
Inventors look to develop more biocompatible nanobodies and will determine the brain permeability potential. They look to expand the application to different strains of alpha-synuclein for the diagnosis and treatment.
Publication
Butler, Y.R., Liu, Y., Kumbhar, R. et al. α-Synuclein fibril-specific nanobody reduces prion-like α-synuclein spreading in mice. Nat Commun 13, 4060 (2022). https://doi.org/10.1038/s41467-022-31787-2
