Gold nanoparticles can reverse brain deficits linked to multiple sclerosis and Parkinson’s disease

Results from phase two clinical trials conducted at UT Southwestern Medical Center showed that a suspension of gold nanocrystals taken daily by patients with multiple sclerosis (MS) and Parkinson’s disease (PD) significantly reversed significantly reduced metabolite deficits linked to energy activity in the brain and resulted in functional improvement. improvements. The results, published in the Journal of Nanobiotechnologycould potentially help bring this treatment to patients with these and other neurodegenerative diseases, according to the authors.

“We are cautiously optimistic that we will be able to prevent or even reverse some neurological disorders with this strategy,” said Peter Sguigna, MD, who leads the active MS trial and is an assistant professor of neurology and investigator at the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

Proper brain function depends on a continuous supply of energy to the cells of this organ via a molecule called adenosine triphosphate (ATP), explained Dr. Sguigna. Age results in a decline in cerebral energy metabolism, evident by a decrease in the ratio of nicotinamide adenine dinucleotide (NAD+) and its partner, nicotinamide adenine dinucleotide + hydrogen (NADH).

However, studies have shown that in neurodegenerative diseases such as MS, PD and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, this decline in the NAD+/NADH ratio is much faster and more severe. Studies in cells, animal models and human patients have suggested that stopping or reversing this energy deficit could lead to a slower decline, or even partial recovery, in patients with neurodegenerative diseases, said the Dr. Sguigna.

To that end, he and his colleagues teamed up with Clene Nanomedicine, a company developing gold nanocrystals into an orally administered therapeutic agent for neurodegenerative diseases, including an experimental treatment called CNM-Au8. These nanocrystals act as catalysts that improve the NAD+/NADH ratio, thereby positively altering the energy balance of brain cells, a phenomenon demonstrated in cellular and animal models in previous studies.

To determine whether CNM-Au8 reached its target in human patients, UTSW researchers recruited 11 participants with relapsing MS and 13 with Parkinson’s disease for two phase two clinical trials, REPAIR-MS and REPAIR- PD. These participants received an initial brain magnetic resonance (MR) spectroscopy scan to determine their baseline NAD+/NADH ratio and levels of other molecules associated with cellular energy metabolism. After taking a daily dose of CNM-Au8 for 12 weeks, testing included a second MRI spectroscopy.

Together, the 24 patients experienced an average increase in their NAD+/NADH ratios of 10.4% from baseline, showing that CNM-Au8 was targeting the brain as expected. Other energy molecules, including ATP, normalized to the group lead, at the end of the treatment, to another potentially beneficial effect.

Using a validated Parkinson’s disease functional outcomes survey, researchers found that study patients with the disease reported improvements in “motor experiences of daily living,” which suggests that taking CNM-Au8 could improve the functional symptoms of their disease. None of the patients experienced serious adverse side effects related to CNM-Au8.

Although these results are encouraging, additional studies are needed, Dr. Sguigna said. REPAIR-MS will continue to recruit participants to see if similar results can be replicated in progressive MS.