Interim results from two phase 2 studies provide evidence that orally delivered CNM-Au8 (gold nanocrystals) have catalytic effects on key bioenergetic metabolites in the brain of patients with MS and Parkinson’s disease (PD). The observed brain metabolic homeostasis may be neuroprotective.
In both MS and PD pathophysiology, CNS bioenergetic failure plays a significant role. CNM-Au8 is a suspension of clean-surfaced, faceted, gold nanocrystals that promotes remyelination and neuroprotection by catalyzing nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) production and reducing oxidative stress. Treatment effects are evaluated using high-resolution 31P-magnetic resonance spectroscopy (31P-MRS). With this quantitative technique, bioenergetic metabolites as well as phospholipid and myelin precursors can be monitored.
Preliminary target engagement data from 2 ongoing open-label imaging trials were presented: REPAIR-MS and REPAIR-PD. Treatment consisted of CNM-Au8 30 mg/day. 7T 31P-MRS was conducted at baseline and after 12-16 weeks of treatment. Results from 4 completers with MS and 6 completers with PD were available. For key bioenergetic markers, percent change from baseline at the end-of-study visit was found to highly correlate to baseline levels. Whole-brain baseline NAD levels that were below the mean significantly increased at the end-of-study visit. On the other hand, baseline NAD levels higher than the mean normalized to mean baseline levels. These dynamics were not only observed for total NAD levels (r2=0.6384; P=0.0056), but also for β-ATP (r2=0.8723; P<0.0001), and several other 31P metabolites. According to the authors, this observation indicates that CNM-Au8 has a homeostatic effect on brain bioenergetics.
Full analyses will be conducted once the 2 trials are completed. Another ongoing study called VISIONARY-MS will further explore the possible neuroprotective effects of the brain metabolic homeostasis that is observed with CNM-Au8 treatment.
- Ren J, et al. MSVIRTUAL2020, P0206.