Here is the 2nd ANN abstract because there were some problems to get it.
Abstract
Objective: To assess neurofilament light chain (NfL) as a biomarker of disease progression and disease modification by PBT434 in a mouse model of multiple system atrophy (MSA).Background: MSA is a fatal neurodegenerative disorder characterized by aggregated α-synuclein in oligodendrocytes. Disease progression is associated with increased NfL in CSF and plasma. Key features of MSA are replicated in the PLP-α-syn transgenic mouse, including progressive striatonigral degeneration and motor deterioration (Refolo et al. 2018). PBT434, a novel small molecule inhibitor of α-synuclein aggregation, was neuroprotective and improved motor function in this model. The relationships between NfL and disease progression in PLP-α-syn transgenic mice and PBT434’s effects are not known
.Design/Methods: Study #1: Plasma and CSF NfL from PLP-α-syn transgenic mice at various stages of disease progression and from healthy controls were measured by single molecule array (Simoa). Study #2: Six-month old PLP-α-syn transgenic mice were provided PBT434 in diet or control diet for six months. CSF and plasma samples were collected at baseline and at the end of the treatment period. Motor behavior was evaluated and brains were preserved for neuropathological analysis.
Results: Study #1: Concentrations of NfL in CSF and plasma changed in parallel with disease progression in the MSA mouse model, with marked increases between 6 and 12 months of age. Study #2: Consistent with previous findings, PBT434-treated MSA mice demonstrated improved performance on the balance beam as compared to control treatment (p<0.05). The correlation between the motor performance and the concentration of NfL in CSF and plasma is under review
Conclusions: NfL concentration in CSF and plasma is a relevant biomarker of disease progression in the PLP-α-syn transgenic MSA mouse model. It may serve as a relevant biomarker for the evaluation of efficacy of disease modifying therapies in MSA including those which reduce α-synuclein aggregation
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- Another abstract in AAN virtual meeting
Another abstract in AAN virtual meeting, page-12
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