Objective: To determine the effects of the nanocatalytic drug, CNM-Au8, on brain energy metabolites in Parkinson’s Disease.

Background: Converging lines of evidence are identifying brain energy dyshomeostasis as a driver of neuronal death in many neurodegenerative diseases, including Parkinson’s Disease (PD). CNM-Au8 is a bioenergetic nanocatalyst, consisting of a suspension of faceted clean-surfaced gold nanocrystals that catalytically improve bioenergetic metabolism in neurons and glial cells. CNM-Au8 catalyzes oxidation of nicotinamide adenine dinucleotide (NADH), an energetic metabolite essential for ATP production, as well as catalyzing the reduction of oxygen radicals.

Method: Seven Tesla ³¹phosphorous magnetic resonance spectroscopy (³¹P-MRS) was used to detect levels of energy metabolites including NAD+, NADH, ATP (b-, a-, and g-), and mono- and diester phospholipids in the brains of 12 PD patients. Whole brain spectra was collected in ~600 voxels at a spatial resolution of 2 cm³ with a full volume coil. A partial volume coil was used to determine the NAD+/NADH ratio by imaging the parietal and occipital lobes bilaterally as a single voxel. Imaging was conducted at baseline (BL) and repeated after 12+ weeks.

Results: CNM-Au8 treatment resulted in homeostatic effects on brain bioenergetic metabolites including improvements in the NAD+/NADH ratio (primary endpoint), and normalization of ATP and NAD levels (secondary endpoints). Patients with ATP and NAD levels less than the BL mean significantly increased whole-brain ATP and NAD levels, while patients with BL levels greater than the mean normalized these levels. Importantly, this relationship was highly significant and consistent for several ³¹P biomarkers: NAD levels, ATP, and several other ³¹P metabolites (r² > 0.6; p < 0.01 for each metabolite). We will report ³¹P-MRS metabolite results, clinical effects on the MDS-UPDRS, and functional correlates between brain metabolic and clinical effects.

Conclusion: Results from this newly completed study are anticipated to provide the first clinical evidence of CNM-Au8 treatment on brain bioenergetic metabolism and support its candidacy as a disease-modifying drug for PD.

A previous preliminary data cut from this trial, consisting of data from 4 MS and 6 PD patients, was presented at the MSVirtual 2020 Meeting.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/homeostatic-improvement-of-brain-bioenergetic-metabolism-in-parkinsons-disease-results-from-a-phase-2-repair-pd-clinical-trial-with-cnm-au8/