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.
To cite this abstract in AMA style:R. Glanzman, J. Ren, Phd, R. Dewey, Iii, A. Rynders, K. Ho, Phd, R. Dewey, JR.. Homeostatic Improvement of Brain Bioenergetic Metabolism in Parkinson’s Disease: Results From A Phase 2 REPAIR-PD Clinical Trial With CNM-Au8 [abstract]. Mov Disord. 2021; 36 (suppl 1). 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/. Accessed December 7, 2023.
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