University of Texas Southwestern Medical Center
Advanced Imaging Research Center, Radiology

Author Of 1 Presentation

Clinical Trials Poster Presentation

P0206 - Effects of nanocatalysis on CNS bioenergetic markers in patients treated with CNM-Au8: Interim results from two Phase 2 31Phosphorous imaging studies (ID 1741)

Presentation Number
P0206
Presentation Topic
Clinical Trials

Abstract

Background

Multiple sclerosis (MS) and Parkinson’s Disease (PD) patients display marked bioenergetic deficits in the CNS. 31Phosphorous magnetic resonance spectroscopy (31P-MRS) is a non-invasive, quantitative imaging technique for monitoring bioenergetic metabolites, as well as phospholipid and myelin precursors. CNM-Au8 is a suspension of clean-surfaced, faceted, gold nanocrystals that catalyze NAD and ATP production and reduce oxidative stress, resulting in remyelination and neuroprotection. Two Phase 2 CNS imaging trials, REPAIR-MS and -PD, were initiated to determine the effects of orally delivered CNM-Au8 on 31P-MRS brain metabolites. An interim analysis of data from completers of these ongoing trials is presented.

Objectives

The objective of this study is to determine the effect of CNM-Au8 treatment on 31P brain bioenergetic metabolites in MS and PD patients.

Methods

7 Tesla 31P-MRS was conducted at baseline (BL) and after 12-16 weeks of CNM-Au8 treatment (30 mg/day, p.o.). A full volume coil was used to collect whole brain spectra in ~600 voxels with a spatial resolution of 2 cm3. Automated analyses of the integrated area of each 31P peak by voxel was normalized to phosphocreatine area and then averaged across voxels for each patient at BL and end of study (EOS). Linear regression determined r2 values for the percentage change from BL for each metabolite versus BL values.

Results

Results for 4 MS and 6 PD completers were analyzed. Percent change from BL at the EOS visit was highly correlated to BL levels for key bioenergetic markers. Patients with nicotinamide adenine dinucleotide (NAD) levels less than the BL mean significantly increased whole-brain NAD levels at the EOS visit, while patients with BL NAD levels greater than the mean normalized levels to the BL mean. Importantly, this relationship was observed for total NAD levels (r2 = 0.6384; p = 0.0056), β-ATP (r2 = 0.8723; p < 0.0001), and several other 31P metabolites, indicating a homeostatic effect of CNM-Au8 on brain bioenergetics. In the 4 MS patients, there were marked correlations for NAD (r2 = 0.9241; p = 0.039), β-ATP (r2 = 0.968; p=0.016), and several other 31P metabolites.

Conclusions

These preliminary results provide the first clinical evidence demonstrating the catalytic effects of CNM-Au8 on key bioenergetic metabolites in MS and PD brains. Full analyses will be conducted once the trials are completed. The brain metabolic homeostasis observed with CNM-Au8 treatment may be neuroprotective, a hypothesis currently being explored in the ongoing VISIONARY-MS study.

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