Evidence for Brain Energy Metabolic Support with CNM-Au8 Treatment: Results from the REPAIR Phase 2 Clinical Trials


Clinical Trials

Poster Number: 36


Robert Glanzman, MD, FAAN, Clene Nanomedicine Inc, Jimin Ren, PhD, University of Texas Southwestern Medical Center, Richard B. Dewey III, MD, University of Texas Southwestern Medical Center, Austin Rynders, RN, Clene Nanomedicine, Inc., Karen Ho, PhD, Clene Nanomedicine, Inc., Michael T. Hotchkin, Clene Nanomedicine, Inc., Richard B. Dewey, Jr., MD, University of Texas Southwestern Medical Center, Benjamin Greenberg, MD, University of Texas Southwestern Medical Center

Converging lines of evidence implicate dysregulated neuronal energy metabolism as a driver of neuronal death in many neurodegenerative diseases, including Parkinson’s Disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of clean-surfaced, catalytically active gold nanocrystals shown to enhance neuronal metabolic energy, reduce oxidative stress, and improve protein homeostasis. CNM-Au8 catalyzes the oxidation of nicotinamide adenine dinucleotide (NADH), an energetic metabolite essential for ATP production, as well as catalyzing the reduction of oxygen radicals.

Seven Tesla 31-phosphorous magnetic resonance spectroscopy (31P-MRS) was used to detect levels of energy metabolites including NAD+, NADH, ATP (alpha-, beta-, and gamma-ATP), and mono- and diester phospholipids in the brains of 13 PD participants and 11 MS participants at baseline and following 12-weeks of treatment with CNM-Au8. Whole brain spectra were 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.

CNM-Au8 treatment resulted in improved brain NAD+/NADH ratio (primary endpoint, paired t-test, p=0.0371), driven by an increase in NAD+ and a decrease in NADH (secondary endpoint, paired t-test, p=0.0264). CNM-Au8 treatment resulted in homeostatic effects on brain bioenergetic phosphorous metabolites including ATP, where study participants with ATP levels less than the baseline mean significantly increased whole-brain ATP levels, while patients with baseline levels greater than the baseline mean decreased levels to the population mean (r2 = 0.711, p<0.0001).

Results from the REPAIR clinical trials demonstrate CNS target engagement with CNM-Au8. These data provide clinical evidence of the effect of CNM-Au8 treatment on brain energetic metabolism and support its candidacy as a disease-modifying therapy for the treatment of neurodegenerative diseases associated with dysregulated neuronal energy metabolism.