CNM-Au8 for multiple sclerosis

Last updated Feb. 28, 2025, by Teresa Carvalho, MS
Fact-checked by Ines Martins, PhD

What is CNM-Au8 for MS?

CNM-Au8 is an oral therapy candidate being investigated as a potential disease-modifying treatment for relapsing and progressive forms of multiple sclerosis (MS).

Developed by Clene Nanomedicine, CNM-Au8 has been investigated in two Phase 2 clinical trials in MS, in which it was given daily in the form of a liquid suspension.

Clene is also testing CNM-Au8 to treat amyotrophic lateral sclerosis and Parkinson’s disease, two other neurodegenerative disorders.

Therapy snapshot

How does CNM-Au8 work in MS?

In MS, the immune system mistakenly launches an inflammatory attack that damages myelin, a fatty sheath that covers nerve fibers and is essential for the efficient conduction of nerve signals. The lost myelin can be replaced by myelin-producing cells called oligodendrocytes, but the inflammation in MS renders the remyelinating process largely inefficient.

CNM-Au8 is an oral, liquid suspension of gold nanocrystals designed to increase energy reserves within nerve cells and oligodendrocytes, while helping to remove toxic substances of cellular metabolism. This is expected to help protect neurons and aid in the generation of myelin by oligodendrocytes.

In animal models of demyelination, CNM-Au8 treatment resulted in a significantly higher energetic capacity and a greater number of myelinated nerve fibers. It also was associated with a significant recovery of physical abilities in mice, evaluated using different locomotor and fine motor tests.

How will CNM-Au8 be administered in MS?

CNM-Au8 is a drinkable therapy available in a dark red/purple-colored liquid suspension. The therapy has been tested at daily doses of 15 mg and 30 mg in an efficacy MS trial. The 30 mg dose was selected for that trial’s open-label extension part.

Whether this dose will also be tested in the planned Phase 3 trial, or ultimately selected for dosing patients in the clinic upon approval, is unknown.

CNM-Au8 in MS clinical trials

After establishing that CNM-Au8 was safe and well tolerated in healthy volunteers, Clene launched two Phase 2 clinical trials — REPAIR-MS (NCT03993171) and VISIONARY-MS (NCT03536559) — to assess the safety and efficacy of CNM-Au8 in people with MS.

REPAIR-MS trial

The REPAIR-MS trial was designed to evaluate the bioenergetic and metabolic impact of the gold nanocrystals in individuals with relapsing forms of MS. Participants were on stable Tysabri (natalizumab) treatment for at least six months, and their disease had been stable for at least three months.

After a four-week screening period, each participant received one of four doses — 7.5 mg, 15 mg, 30 mg, or 60 mg — of CNM-Au8 in a liquid suspension. These were given daily for 12 weeks, or about three months.

The study’s main goal was to measure changes in the ratio of two metabolic markers, NAD+ and NADH, that indicate how much energy cells produce. The ratio was measured using 31-phosphorous magnetic resonance spectroscopy, known as 31P-MRS, a noninvasive brain imaging technique.

Combined data from REPAIR-MS and REPAIR-PD (NCT03815916), a similar Phase 2 trial involving people with Parkinson’s disease, demonstrated that patients had a 10.4% increase in energy metabolism after 12 weeks of treatment. Altogether, these trials involved 24 people: 11 patients with relapsing-remitting MS (RRMS) and 13 with Parkinson’s. 

Among the MS patients, the treatment also improved measures of cognition, visual function, dexterity, and walking speed.

The trial was reopened to include an additional group of 15 adults with progressive forms of MS, both primary progressive MS and nonactive secondary progressive MS. All of the new participants were on stable treatment with either an anti-CD20 antibody like Ocrevus (ocrelizumab) or an S1P modulator such as Mayzent (siponimod) for at least 48 weeks, or nearly one year.

As in the earlier part, patients were to receive daily oral CNM-Au8 for 12 weeks, with the main goal of assessing the effects of treatment on brain energy metabolites.

VISIONARY-MS trial

The VISIONARY-MS trial sought to test the remyelination potential of CNM-Au8 in people with RRMS and stable disease — meaning patients who hadn’t had a relapse or new MRI activity in at least six months.

All participants had chronic optic neuropathy, or damage to the optic nerve that transmits signals between the eye and the brain, which resulted in vision problems. They were randomly assigned to receive daily CNM-Au8 at a dose of 15 mg or 30 mg, or a placebo, for up to 48 weeks. Nearly all patients (92%) were also being treated with background MS disease-modifying therapies.

The trial’s main goal was to assess changes in a vision test called LCLA, for low contrast letter acuity, after 48 weeks. This is an eye test similar to the common test performed by an optometrist or ophthalmologist in which a patient reads lines of increasingly smaller letters. The LCLA uses a chart with low contrast between the letters and the background, which helps to assess the type of visual impairment experienced by someone with optic nerve damage.

While the trial initially planned to enroll 150 participants, Clene decided to conclude VISIONARY-MS early due to pandemic-related challenges that prevented in-person visits; that limited the number of participants to 73.

Top-line data, which excluded findings from 10 patients primarily due to testing errors in one medical center, showed that CNM-Au8 resulted in significant improvements in LCLA scores compared with the placebo. After 48 weeks, LCLA scores in the affected eye were 3.13 points higher with the experimental therapy, which corresponded to being able to read one additional line of letters.

Patients demonstrated significant improvements in the modified MS Functional Composite scale, a combined measure of LCLA scores in the affected and non-affected eye, as well as in dexterity, walking speed, and cognition. They also showed significant improvements in all individual components except walking speed.

CNM-Au8 outperformed the placebo on measures of visual evoked potentials, which assess the strength and speed of the nerve signals that carry data from the eyes to the brain. Treatment also helped stabilize brain structures and preserve the integrity of the myelin sheath.

VISIONMS-LTE trial

After completing the VISIONARY-MS trial, 55 patients chose to enter an open-label extension study called VISIONMS-LTE (NCT04626921), in which all received the 30 mg dose of CNM-Au8 for up to 96 weeks, or nearly two years. This totaled nearly three years of treatment for those initially assigned CNM-Au8 in the main trial.

Data showed sustained gains across most of the trial’s efficacy measures in the group of patients who were on CNM-Au8 the entire time. For example, these patients could read four more letters on the LCLA eye chart across both eyes from the end of the main trial to the end of the extension — a significant, 8.7-letter improvement from pretrial scores.

Cognition, as assessed by the Symbol Digit Modality Test (SDMT), improved by 3.11 points during the extension, and by a total of 8.03 points when both the main trial and extension periods were considered.

The improvements in mobility and dexterity observed in the main trial were maintained throughout the extension, and patients also showed long-term increases in markers of myelin repair and nerve function.

For those who were initially given the placebo and transitioned to CNM-Au8 in the extension, significant improvements in most of these measures were also observed, which were generally consistent with the benefits seen in people originally given CNM-Au8.

Common side effects of CNM-Au8

CNM-Au8 has been well tolerated in MS clinical trials. Most side effects were transient and mild to moderate in severity. No serious adverse events or treatment discontinuations related to the therapy have been reported to date.

The most commonly reported side effects include:

• headache
• upper respiratory infection
• urinary tract infection.

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