A proprietary and investigational agent consisting of pure clean-surfaced faceted gold nanocrystals suspended in buffered pharmaceutical grade water (CNM-Au8; Clene Nanomedicine, Salt Lake City, UT) is 1 of 3 agents initially chosen to be tested in a platform trial for treatment of amyotrophic lateral sclerosis (ALS). In the Healey Platform trial, multiple agents will be tested using a single set of inclusion/exclusion criteria, centralized randomization and assessment of participant data, and a shared placebo group.
Another 5 clinical trials of the gold nanoparticle are underway. Of these, 3 are proof-of concept studies that will use 7 T MRI spectroscopy to confirm target engagement and cellular activity of gold nanoparticles within the brains of individuals with Parkinson’s disease (PD), ALS, or multiple sclerosis (MS) (NCT03993171, NCT03815916, NCT03843710. A phase 2 trial (VISIONARY-MS [NCT03536559]) is measuring effects on vision in people with MS who have chronic optic neuropathy, and another phase 2 trial (RESCUE ALS [NCT04098406] is investigating safety of the gold nanoparticles and any effect on preserving the number of motor units in the spinal cord of participants with ALS, which is known to predict ALS progression.
Robert Glanzman, MD, FAAN and chief medical officer of Clene Nanomedicine told Practical Neurology, “This is the first therapeutically active nanoparticle in which the crystal structure of a catalytically active metal is the actual treatment modality. We are excited to be testing this nanoparticle formulation of gold in 6 clinical trials for ALS, PD, and MS. We believe that by providing cells with the energy they need when under stress, we can promote recovery for patients with neurodegenerative diseases and significant unmet medical needs.”
Preclinical studies using in vitro or mouse models of demyelination, PD, and ALS, demonstrated remyelination and recovery of neurons from induced injury or genetic causes, in the case of ALS. Either pre- or postinjury treatment with gold nanoparticles resulted in either full recovery of myelination (in models of demyelination), neuronal preservation and recovery (in Parkinson’s models), and recovery of motor neurons in animal models of ALS that also extended lifespan of the treated animals.
The nanoparticle consists of gold atoms suspended in pharmaceutical grade water, arranged into highly faceted crystals of approximately 10 to 13 nm diameter. The gold acts as a nanocatalyst to transfer and/or receive electrons, thereby improving the efficiency of bioenergetic reactions and reducing free radicals known to cause oxidative stress, thereby contributing to energy production of cells that are under oxidative stress.
Stephen M. Gollomp, MD, and Paul G. Mathew, MD, DNBPAS, FAAN, FAHS
Alexis Dallara-Marsh, MD