Nearly 1 million people in the United States are living with multiple sclerosis—an inflammatory, demyelinating disease of the central nervous system that is the most common (non-traumatic) cause of neurological disability in young adults. Approximately one in three people with multiple sclerosis have developed a progressive form of the disease called relapsing multiple sclerosis, for which there are no approved, effective therapies, leading to significant loss of quality of life for these patients. 

Clene Nanomedicine, Inc., a clinical-stage biopharmaceutical company, recently announced the presentation of interim results from their Phase II clinical trials, which involve several hundred participants who are living with the condition that the new medication is meant to treat. The trials have thus far demonstrated the effects of its lead experimental therapeutic CNM-Au8 in patients with either relapsing multiple sclerosis or Parkinson’s disease. The preliminary data from the Phase II studies REPAIR-MS and REPAIR-PD demonstrate CNM-Au8 modulates key molecules essential for energy flow and metabolism, such as nicotinamide adenine dinucleotide (NAD+), in the central nervous systems of these patients. Full analyses will be conducted once the Phase II clinical trials are complete.

“We believe these interim data represent the first clinical evidence of CNM-Au8’s ability to positively impact key bioenergetic metabolic markers in the brains of multiple sclerosis and Parkinson’s disease patients, two diseases in which central nervous system bioenergetic failure is known to play a significant role in disease pathophysiology,” said Robert Glanzman, MD, FAAN, Chief Medical Officer of Clene. 

Multiple sclerosis manifests as a chronic inflammatory disease in the central nervous system, causing levels of important molecules for energy flow and metabolism like NAD+ to become altered. This leaves cells of the central nervous system starving for sources of these vital molecules that, ultimately, results in damage to the protective sheath surrounding neurons essential for conducting electrical signals called myelin. Studies have shown that administering doses of NAD+ precursors, like nicotinamide mononucleotide or nicotinamide riboside, improve multiple sclerosis in animal models.

The experimental neuro-therapeutic CNM-Au8 formulated by Clene Nanomedicine, Inc., is a nano-catalytic, meaning it works in stressed cells by enhancing key metabolic reactions by increasing energy reserves while independently decreasing destructive activity caused by harmful reactive molecules. The hope for this treatment approach is that CNM-Au8 will not only prevent further damage to the conductive and protective myelin wrapped around neurons but will repair previously damaged myelin and, in the process, improve the survival and function of neurons.

(Robinson et al., Scientific Reports | 2020) A microscopic image of a representative CNM-Au8 nanoparticle. CNM-Au8 is a stable, aqueous suspension of gold (Au) nanoparticles in the shape of hexagonal bi-pyramids, pentagonal bi-pyramids, octahedrons, and tetrahedrons, as analyzed by transmission electron microscopy (TEM). Each nanocrystal has approximately 68,000 Au atoms per nanocrystal with a 13 nm median diameter.

In preclinical studies, which are performed in the lab on animal or cell models prior to testing in humans, CNM-Au8 prolonged survival of nerve cells in the central nervous system of mice and showed effectiveness in regenerating myelin. CNM-Au8 also showed safety and tolerability in Phase I clinical studies that involved healthy volunteers. For these reasons, Clene Nanomedicine received approval from the US Food and Drug Administration (FDA) to conduct Phase II clinical studies of this experimental medication for reversing remyelination failure in patients with multiple sclerosis.

REPAIR-MS and REPAIR-PD, the key studies involving CNM-Au8, examine the effects and safety of this drug in patients who have been diagnosed with multiple sclerosis within 15 years of screening or in patients with Parkinson’s disease who have been diagnosed within three years of screening. In these studies, the participants receive a dose that can consist of a 15 or 30 mg orally delivered dose of the nanocrystal suspension daily each morning for 12 weeks.

The objective of this study is to demonstrate target engagement for CNM-Au8 with critical molecules like NAD+ that facilitate energy flow and metabolism in the central nervous systems of patients with multiple sclerosis and Parkinson’s disease. The study is taking place at the University of Texas Southwestern Medical Center with a team of internationally recognized experts in brain imaging and treatment of disorders of the central nervous system.

“We generally receive the same questions regarding CNM-Au8: how do you know that CNM-Au8 gets to the brains of people, especially people with neurodegenerative diseases, and if it does, how do you know it will have bioenergetic effects in patients?” said Dr. Glanzman.

The interim results from 4 multiple sclerosis and 6 Parkinson’s disease patients that completed the clinical trials demonstrate significant engagement of CNM-Au8 with targets in the central nervous system. The data indicate improvements in the levels of important molecules for energy flow and metabolism in the central nervous system that includes NAD+, indicating a balancing effect of CNM-Au8 on how energy is transformed and used in the brain.

“These data from REPAIR-MS and REPAIR-PD indicate that CNM-Au8 is working mechanistically to address a foundational challenge common to many neurodegenerative diseases, namely that stressed or failing neurons need additional energy for their survival, repair, and improved function,” said Rob Etherington, President and CEO of Clene.

“We now have insights that CNM-Au8 is driving bioenergetics within the brain, which is a foundational insight for the further development of Clene’s neurorepair clinical programs. Results from these and our other ongoing studies aim to establish Clene as a pioneer in therapeutic neurorepair and neuroprotection. We believe these preliminary data may suggest the potential for CNM-Au8 to treat millions of individuals worldwide suffering from multiple sclerosis and Parkinson’s disease.”