Phase 2 trial findings support larger study of CNM-Au8 for Parkinson’s

Better brain energy levels seen with oral gold nanocrystal suspension therapy

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Treatment with CNM-Au8, an investigational gold nanocrystal suspension therapy, boosted energy production in the brains of people with Parkinson’s disease and multiple sclerosis (MS) in a pair of Phase 2 trials, indicating the medication works as intended.

Findings also suggest functional gains in treated Parkinson’s patients. However, the proof-of-concept trial was not designed to detect clinical changes, and larger studies are warranted, according to scientists.

“We are cautiously optimistic that we will be able to prevent or even reverse some neurological disabilities with this strategy,” Peter Sguigna, MD, a researcher, assistant professor of neurology at the University of Texas Southwestern, and a study author, said in a university news release.

Both trials were conducted at that university and supported by Clene Nanomedicine, CNM-Au8’s developer.

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Findings were detailed in the study, “Evidence of brain target engagement in Parkinson’s disease and multiple sclerosis by the investigational nanomedicine, CNMAu8, in the REPAIR phase 2 clinical trials,”  published in the Journal of Nanobiotechnology and also supported by Clene.

The brain requires large amounts of energy to perform its many functions. This relies on a continuous supply of adenosine triphosphate (ATP), a molecule that’s broken down to provide the majority of cellular energy in the body.

These high demands also mean that the brain is particularly vulnerable when not enough energy is being provided. Energy-deficient cells are prone to damage, dysfunction, and death.

It is normal for brain energy metabolism to decline with age, but research indicates that this process is faster and more severe in people with neurodegenerative diseases such as Parkinson’s, MS, or amyotrophic lateral sclerosis (ALS).

Such declines in energy balance are reflected by a decreased ratio of the molecules nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide + hydrogen (NADH), which can be measured using advanced imaging techniques.

CNM-Au8 is a liquid oral suspension of gold nanocrystals that are believed to facilitate the conversion of  NADH to NAD+, thereby increasing ATP production and positively affecting the brain’s energy balance. In turn, this is expected to protect nerve cells and slow disease progression.

Preclinical studies demonstrated its possible therapeutic benefits: CNM-Au8 was associated with nerve cell protection and improved motor function in a rat model of Parkinson’s disease.

Two proof-of-concept trials — REPAIR-PD (NCT03815916) and REPAIR-MS (NCT03993171) — were launched in 2019 to evaluate the effects of CNM-Au8 on brain in 13 adults with idiopathic (of unknown cause) Parkinson’s and 11 with relapsing-remitting MS.

Parkinson’s participants, with a mean age of 65.9, had been living with the disease for a mean of 1.5 years at enrollment (17.2 months since Parkinson’s diagnosis), and were on standard Parkinson’s treatments. About half, 54%, of these 13 adults were men.

All participants in both trials received oral CNM-Au8 (15 mg or 30 mg) once daily for 12 weeks, or about three months.

Proof-of-concept trials support moving CNM-Au8 into Phase 3 studies

Consistent with previous reports, combined results from the two trials showed that NAD+/NADH ratios significantly increased by an average of 10.4% after three months of treatment, indicating that the therapy’s use led to improvements in the brain’s energetic profile, its intended effect and meeting the study’s main goal.

Analyzed separately, both Parkinson’s patients and MS patients showed increases in the NAD+/NADH ratio. But these findings failed to reach statistical significance, “likely due to the limited sample size,” the researchers noted, meaning the small number of enrolled patients.

Other molecules related to cellular energy production, including ATP, also normalized by the end of treatment. Participants with low ATP levels at the study’s start exhibited increases, whereas those with initial elevated levels experienced reductions.

Such a finding is important given that “both increased and decreased levels of brain ATP are indicative of disease state,” the researchers wrote.

Parkinson’s patients also exhibited significant improvements in scores on Part 2 of the Movement Disorders Society – Unified Parkinson’s Disease Rating Scale, reflecting an easing of Parkinson’s motor symptoms on daily life.

Researchers attribute this finding, largely driven by improvements during the first month of treatment, to patients’ expectations of improving with treatment, known as a placebo effect. Other measures of clinical function did not change.

The treatment was generally well tolerated, with no severe adverse side effects observed.

“Results from the REPAIR studies indicate that … brain energy metabolism is favorably modulated in individuals with MS or PD [Parkinson’s disease],” the researchers concluded. “CNM-Au8 represents a strong candidate drug with appropriate target engagement and safety data supporting its advancement Phase 3 trials for the treatment of neurodegenerative disease.”