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BOSTON -- Gold nanoparticles in an oral suspension helped patients with relapsing multiple sclerosis (MS) preserve ocular and overall function when added to standard medications in a phase II trial, a researcher said here.

Those assigned to the product, dubbed CNM-Au8, saw an improvement in low-contrast letter acuity (LCLA) of 3.13 letters relative to a placebo group (P=0.056), according to Michael Barnett, MBBS, PhD, of the University of Sydney in Australia.

Scores on the modified MS Functional Composite (MSFC) instrument, which combines tests of upper- and lower-limb function plus visual acuity, also significantly favored the drug, Barnett told attendees at the American Academy of Neurology annual meeting.

Mean MSFC scores increased by nearly 4 points with CNM-Au8, versus approximately 0.7 points with placebo (P=0.020). Because the investigators prespecified a P value threshold of 0.10 for statistical significance, both efficacy endpoints were judged to have been met, Barnett said.

And this was achieved with only half of the trial's originally projected enrollment. The group had hoped to randomize 150 patients, but thanks to pandemic-related difficulties with recruitment, they settled for just 73 in order to obtain timely results.

Gold has a long and fascinating history in medicine going back to ancient times. More recently, gold salts have been used to treat and some inflammatory diseases, notably . With CNM-Au8, however, the presumed mechanism of action is different and better defined.

To explain, Barnett first described the basic cellular pathology of MS. Initially, an autoimmune reaction strips the myelin sheath from the neuronal axon. This leads to the slow strangulation of mitochondria in the neuron, depriving the axon of needed energy. Gold catalyzes activity of nicotinamide adenine dinucleotide, a key co-factor in generating adenosine triphosphate. The idea is that CNM-Au8 -- eight-sided, nanoscale gold crystals that can pass from the alimentary tract into circulation -- can thus block axonal degradation and even promote remyelination and thus preserve nerve cells' normal function. ( such as amyotrophic lateral sclerosis [ALS] and Parkinson's disease may also benefit from this approach.)

The 73 patients in the 48-week phase II trial, called , were randomized in equal numbers to CNM-Au8 or placebo. All had chronic optic neuropathy as a condition of enrollment. Participants' mean age was about 39, with Expanded Disability Status Scale scores averaging about 1.7, and mean disease duration of 5-6 years. Nearly all were on some form of disease-modifying drug therapy, and about half were taking a biologic agent. These were allowed to continue in the trial.

Improvements seen with the gold product were most apparent with LCLA in the most-affected eye and in the 9-hold peg test for the dominant hand. There was no effect on non-dominant hand performance, and changes in walking ability (via the 25-foot walk test) did not differ significantly between study arms.

Biomarker endpoints also favored the active treatment. Electrical activity in the optic nerve was markedly increased, and only slight diminution in whole-brain fractional anisotropy in MRI analyses was observed. In the placebo group, both optical electrical activity and fractional anisotropy declined. Other assessments suggested that myelin integrity was at least preserved over the trial's 48 weeks, with hints that remyelination may have slightly outstripped ongoing demyelination.

In a separate study presented at the same AAN session, Sabrina Paganoni, MD, PhD, of Massachusetts General Hospital in Boston, reported results with CNM-Au8 in a so-called . In this ongoing and expanding trial, CNM-Au8 was one of seven different drugs being tested under the same protocol and with the same endpoints, the primary being 24-week change in a standard evaluation of overall ALS severity.

CNM-Au8 did not show a benefit by that measure, Paganoni reported. But some secondary outcomes did, notably a composite of death and permanent assisted ventilation. As such, the investigators determined that a phase III study is warranted.

At this point, developer Clene Nanomedicine of Salt Lake City, has not finalized a plan for further testing in either MS or ALS, although open-label extensions in both phase II studies are still in progress.

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