Dosing Begins in Phase 2 Trial of CNM-Au8, Potential Therapy for Dopaminergic Neurons

A pilot Phase 2 study evaluating CNM-Au8, an investigational Parkinson’s treatment aiming to protect nerve cells, has started dosing patients, the therapy’s developer, Clene Nanomedicine, announced.

The open-label REPAIR-PD (NCT03815916) clinical trial is enrolling up to 24 people, ages 30 to 80 and diagnosed within the past three years, at its one site at the University of Texas Southwestern Medical Center.

“We are excited to be advancing CNM-Au8 clinically into Parkinson’s patients starting with the REPAIR-PD Phase 2 study” Rob Etherington, president and CEO of Clene, said in a press release.

Parkinson’s disease is characterized by the death of dopaminergic neurons in two brain regions, the striatum and the substantia nigra. These nerve cells rely on large amounts of energy to function, which is provided by mitochondria, the cell’s powerhouses. Failure to provide the energy that cells need contributes to their death.

Oxidative stress, an imbalance between the production of harmful free radicals and the ability of cells to detoxify them, is another hallmark of Parkinson’s disease. These free radicals, or reactive oxygen species, are produced during certain metabolic reactions that involve mitochondria, and can damage cells.

CNM-Au8 is a suspension of nanocrystalline gold designed to increase the production of energy. Specifically, it works by increasing the speed of conversion between two molecules — nicotinamide adenine dinucleotide (NADH) to its oxidized form (NAD+) — resulting in greater production of energy in the form of ATP (adenosine triphosphate, an energy-carrying molecule of cells).

In addition, CNM-Au8 has antioxidant properties that may help to protect cells against oxidative stress.

Preclinical (in the lab) data showed that CNM-Au8 aided the survival of dopaminergic neurons, and helped prevent the loss of mitochondria.

In a rat model of Parkinson’s disease, treatment with CNM-Au8 improved the animal’s motor activity compared to control (untreated) mice. Of note, rats treated with CNM-Au8 in this test showed better results than did rats given carbidopa/levodopa, a standard Parkinson’s therapy.

“Our preclinical data with CNM-Au8 demonstrated improvements in neuronal bioenergetics, which may improve the survival of dopaminergic neurons in patients with PD [Parkinson’s disease], thereby helping slow the progression of this devastating disease,” Etherington said.

A Phase 1 clinical trial involving healthy volunteers (NCT02755870) found CNM-Au8 to be safe.

In the REPAIR-PD study, patients will first undergo a four-week screening period, after which they will drink two ounces of CNM-Au8 daily each morning for 12 weeks. Treatment will be followed by a four-week follow-up period.

The study’s primary outcome is to determine improvements in oxidative stress in the central nervous system (brain and spinal cord), assessed by the ratio of NAD+/NADH measured using magnetic resonance spectroscopy (MRS).

Additional (secondary) measures include assessing the effects of CNM-Au8 on energy production, and nerve cell metabolism.

“The objective of the REPAIR-PD Phase 2 study is to demonstrate improvements in brain bioenergetic metabolism in Parkinson’s disease patients treated with CNM-Au8. Participants will undergo ³¹phosphorous magnetic resonance spectroscopy (³¹P-MRS) imaging to show how treatment with CNM-Au8 results in improvements in brain metabolic and membrane biomarkers,” said Robert Glanzman, MD, chief medical officer of Clene.

Results from the REPAIR-PD trial are expected by mid-2020.