Synonyms: Gold nanocrystals
Therapy Type: Other
Target Type: Metals, Other (timeline)
Condition(s): Parkinson's Disease, Amyotrophic Lateral Sclerosis
U.S. FDA Status: Parkinson's Disease (Phase 2), Amyotrophic Lateral Sclerosis (Phase 2/3)
Company: Clene Nanomedicine, Inc.
CNM-Au8 is a preparation of pure elemental gold nanoparticles in a drinkable bicarbonate solution. The faceted crystals have a median diameter of 13 nm, slightly smaller than a ribosome. Their surfaces catalyze oxidation-reduction reactions, including the conversion of NADH to NAD+ (Huang et al., 2005). NAD+ is an essential cofactor for ATP generation and a cell metabolic sensor. The rationale for the therapeutic use of gold nanocrystals is that they may help ameliorate cellular-energy deficits and oxidative stress characteristic of multiple neurogenerative diseases.
Other gold nanoparticles have been reported to have reactive oxygen-scavenging, anti-oxidant, and anti-inflammatory activity, including in cell models of Aβ toxicity (e.g. Du et al., 2013; Li et al., 2017; Chiang et al., 2021).
In a preclinical study, CNM-Au8 increased NAD+ and ATP concentrations in cultured neurons and glia, and promoted remyelination and recovery of motor function in two mouse models of multiple sclerosis (Robinson et al., 2020).
In 2015-2016, Clene ran a placebo-controlled Phase 1 study of single and multiple doses of CNM-Au8. It enrolled 86 healthy volunteers, who received 15, 30, 60, or 90 mg single doses, or the same daily doses for 21 days. In its communications, the company reports that drug-related adverse events were neural/gastrointestinal and mild, with none leading to discontinuation in study (see slide 16 in Feb 2021 investor presentation).
In July 2019, the U.S. FDA granted CMN-Au8 orphan drug designation for ALS.
In December 2019, a Phase 2 trial began enrolling 42 ALS patients in two centers in Australia. Participants must be within two years of symptom onset, or one year of diagnosis, and are taking 30 mg drug or a placebo once daily for 36 weeks. The primary endpoint is change from baseline to 36 weeks in an electrophysiological measure of motor neuron function, a biomarker that predicts ALS disease progression. Other endpoints include clinical measures of function, disease progression, and health care utilization. Completion is expected in 2021, and participants who complete the trial can enter a 48-week open-label extension. For trial details, see Vucic et al., 2021.
In July 2020, a Phase 2/3 multicenter study began testing CMN-Au8 as part of Massachusetts General Hospital’s Healy ALS Trial Platform. It is testing four experimental treatments in parallel under a single protocol at 54 locations in the U.S. In the CNM-Au8 arm of the trial, an estimated 160 ALS patients are randomized to 30 or 60 mg daily or matching placebo in a 3:1 ratio. The primary outcome is change in severity after 24 weeks, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary outcomes include respiratory function, muscle strength, and survival. The study is enrolling by invitation, with completion slated for October 2021. Outside of this trial, an immediate access protocol is making the drug available to up to 30 patients at MGH.
In December 2019, two open-label pilot trials began to study CNS metabolic effects of CNM-Au8 in people with Parkinson’s disease and multiple sclerosis. Conducted at University of Texas Southwestern Medical Center, the studies each enroll 30 patients into a three-month course of 7.5 to 60 mg daily. The primary outcome is the brain’s NAD+/NADH redox ratio as measured by magnetic resonance spectroscopy imaging. A similar trial in 24 people with ALS will start in April 2021.
A placebo-controlled Phase 2 trial is ongoing in people with MS, as is an open-label extension for it. The study is assessing the drug’s effect on optic nerve demyelination.
For details on CNM-Au8 trials, see clinicaltrials.gov.
Last Updated: 23 Feb 2021
- Vucic S, Kiernan MC, Menon P, Huynh W, Rynders A, Ho KS, Glanzman R, Hotchkin MT. Study protocol of RESCUE-ALS: A Phase 2, andomised, double-blind, placebo-controlled study in arly ymptomatic amyotrophic lateral sclerosis patients to assess bioenergetic atalysis with CNM-A8 as a mechanism to slow diseas progression. BMJ Open. 2021 Jan 11;11(1):e041479. PubMed.
- Huang X, El-Sayed IH, Yi X, El-Sayed MA. Gold nanoparticles: catalyst for the oxidation of NADH to NAD(+). J Photochem Photobiol B. 2005 Nov 1;81(2):76-83. Epub 2005 Aug 25 PubMed.
- Du L, Suo S, Wang G, Jia H, Liu KJ, Zhao B, Liu Y. Mechanism and cellular kinetic studies of the enhancement of antioxidant activity by using surface-functionalized gold nanoparticles. Chemistry. 2013 Jan 21;19(4):1281-7. Epub 2012 Dec 11 PubMed.
- Li J, Zhang J, Chen Y, Kawazoe N, Chen G. TEMPO-Conjugated Gold Nanoparticles for Reactive Oxygen Species Scavenging and Regulation of Stem Cell Differentiation. ACS Appl Mater Interfaces. 2017 Oct 18;9(41):35683-35692. Epub 2017 Oct 4 PubMed.
- Chiang MC, Nicol CJ, Lin CH, Chen SJ, Yen C, Huang RN. Nanogold induces anti-inflammation against oxidative stress induced in human neural stem cells exposed to amyloid-beta peptide. Neurochem Int. 2021 May;145:104992. Epub 2021 Feb 17 PubMed.
- Robinson AP, Zhang JZ, Titus HE, Karl M, Merzliakov M, Dorfman AR, Karlik S, Stewart MG, Watt RK, Facer BD, Facer JD, Christian ND, Ho KS, Hotchkin MT, Mortenson MG, Miller RH, Miller SD. Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis. Sci Rep. 2020 Feb 11;10(1):1936. PubMed.
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