Discussion
PD, Parkinson’s disease
DISEASE
The objective of our study was to demonstrate brain target engagement of orally administered CNM-Au8 in participants with PD or MS using 7T Limitations of our study include the relatively small number of participants in the REPAIR trials. In addition, the studies had to be terminated after evaluating only one dose of CNM-Au8 due to enrollment challenges associated with the COVID-19 pandemic. While future studies with larger cohorts of participants using brain metabolite imaging to evaluate CNM-Au8 treatment effects are warranted, there were several important observations that these studies afforded, despite their small size.A previous The REPAIR studies also extend the findings of the recent NADPARK study, which reported that elevating brain total NAD levels by dietary supplementation with a high-dose NAD precursor in 30 participants with PD for 30 days was associated with mild clinical improvement, increased brain glucose metabolism, and decreased inflammatory cytokines in serum and CSF [The REPAIR studies also demonstrated significant effects of CNM-Au8 on ATP levels and on the phosphorylation potential using the full volume coil. Global assessment of brain metabolite changes may provide a measure of the overall burden of disease on the brain, independent of specific brain regions, and thus be more comparable across studies and disease states [We believe these observations demonstrate an important homeostatic energetic effect of CNM-Au8 in these patient populations. Both increased and decreased levels of brain ATP are indicative of disease state, in both PD and MS. In PD, a low ATP/Pi ratio is seen in Parkinson’s disease [This short-duration study was underpowered to detect clinical benefit with CNM-Au8 treatment, and thus the finding of no significant clinical benefit (as manifested by stable MDS-UPDRS total scores and APDM gait/balance parameters) was anticipated. We attribute the statistically significant improvement in MDS-UPDRS part 2 (driven by improvement at 4 weeks) to a placebo effect induced by expectation of benefit by subjects who knew they were taking active drug. Historically, symptomatic effects, i.e., effects with short-lived beneficial impact that converge to the level of placebo with time and that lack evidence of longer-term neuroprotection, have confounded outcome measure interpretation for putative neuroprotective drugs [