All that glitters

SALT LAKE CITY—February saw biopharmaceutical company Clene Nanomedicine Inc. share news of preclinical research published in Scientific Reports regarding its CNM-Au8 gold nanocrystals in animal models of multiple sclerosis (MS).

CNM-Au8 is a concentrated, aqueous suspension of nanocrystalline gold that “acts catalytically to support important intracellular energetic reactions,” as explained in a Clene press release. This product has shown remyelination and neuroprotective effects in preclinical models, and safety in Phase 1 studies in healthy volunteers. In preclinical neuronal cultures, treatment with CNM-Au8 improved neuronal survival, protected neurite networks, decreased intracellular levels of reactive oxygen species, and boosted mitochondrial capacity to respond to cellular stress. In rodent models of amyotrophic lateral sclerosis (ALS), MS and Parkinson’s disease, oral CNM-Au8 improved functional behaviors compared to placebo. At present, Clene is investigating this treatment in six Phase 2 clinical studies as a therapy for ALS, Parkinson’s disease and non-active, relapsing MS.

In this most recent study, oral administration of CNM-Au8 in mice that had been treated with cuprizone (a copper-chelating agent that causes demyelination) resulted in improved motor functions in both open field and kinematic gait tests. Co-cultured central nervous system cells demonstrated elevated levels of nicotine adenine dinucleotide, elevated total intracellular ATP levels, elevated extracellular lactate levels, and upregulation of myelin-synthesis related genes, leading to functional myelin generation.

Dr. Robert Glanzman, chief medical officer of Clene Nanomedicine, commented, “We are gratified at the publication of these data. These results establish the rationale for our ongoing Phase 2 clinical trial, VISIONARY-MS, which is designed to demonstrate the efficacy of CNM-Au8 for the treatment of chronic optic neuropathy in patients with non-active relapsing MS.”

Multiple sclerosis is an inflammatory CNS disease characterized by attacks of neurological disability, which can present as loss of vision, numbness, tingling, dizziness, difficulty walking and/or paralysis. MS results from the loss of myelin sheaths around neurons.

As Clene Nanomedicine explains on its website, “neurons process information through an energetic and efficient network via nerve fibers called axons. Information travels through this network via electrical signals to enable cognition and physical function. To support this signaling, the brain needs substantial energy, consuming more than 25 percent of the metabolic resources of the body. In neurodegenerative diseases, metabolic activity becomes impaired in neurons resulting in debilitating loss of neurologic function. In addition to neurons, the brain cells that provide metabolic support to neurons and enable fast axonal signaling (oligodendrocytes) are highly energetically dependent and can become compromised in disease such as multiple sclerosis. In multiple sclerosis, the body attacks the protective sheath around axons, called myelin, that is generated by oligodendrocytes.”

Clene’s approach, nanocatalysis, boosts energetic support for neurons and oligodendrocytes by increasing cellular energy reserves and improving neuronal function and survival, in addition to supporting remyelination.

“This publication demonstrates that CNM-Au8 (clean-surfaced, faceted gold nanocrystals) are capable of actively catalyzing cellular reactions necessary for therapeutic remyelination. These results further validate our entirely new approach using therapeutic gold nanocatalysts as a mechanism to support the cellular viability and enhanced function of neurons and oligodendrocytes. CNM-Au8 is one of a limited number of drugs being developed which have demonstrated remyelination capabilities. We believe these data exemplify a strong step forward in the development of a treatment to improve function in the lives of more than one million people living with MS in the U.S.,” Dr. Karen Ho, director of Translational Medicine and corresponding author for the Scientific Reports article, said in a press release.

Of the almost 1 million individuals in the United States that have MS, according to a National MS Society study, roughly 30 percent of those have a non-active, progressive form of the disease for which there are no approved therapies.

As the authors report in the paper, “The currently available FDA-approved drugs for the treatment of MS act to suppress the recurrent autoimmune attack on myelin during disease progression. These drugs generally limit disease progression by reducing the frequency and intensity of autoimmune attacks. A remyelinating therapy, acting in concert with, or independently of, immunosuppressant drugs, opens up the possibility of restoration of functions that were previously impaired or lost due to MS disease activity, thereby improving patients’ quality of life and potentially reversing disease progression.”