Nanocrystalline Gold Treatment Slows Clinical Decline in Amyotrophic Lateral Sclerosis

New data from the open-label extension trial of the phase 2 RESCUE-ALS study (NCT04098406) for amyotrophic lateral sclerosis (ALS) suggest nanocrystalline gold (CNM-Au8; Clene Nanomedicine, Salt Lake City, UT) slows clinical decline. 

RESCUE-ALS is a phase 2 study that is not powered for statistical analysis of survival. Using the European Network for the Cure of ALS (ENCALS) model as a prognostic marker, however, there has been a 70% slower rate of clinical decline for participants (n=45) in the open-label extension study at this time.

In the 36-week blinded period, individuals treated with nanocrystalline gold vs placebo had slowed disease progression (P=.013). A lower proportion of those treated with nanocrystalline gold had a 6-point decline in the ALS Functional Rating Scale Revised (ALSFRS-R) (P=.035). Improved quality of life with nanocrystalline gold vs placebo was also observed, as measured by the ALS Specific Quality of Life (ALSSQOL-SF) questionnaire (P=.018). Treatment was well tolerated with no serious adverse events occurring over the 36 weeks of the study.

Matthew Kiernan, PhD, DSc, FRACP, FAHMS, Bushell Chair of Neurology and co-director of the Brain and Mind Centre, University of Sydney said “Having worked in this field for 30 years and participated in multiple clinical trials, I feel a much greater sense of optimism regarding this phase 2 trial. We are grateful to the participants, who have remained in the study during a difficult time through the COVID pandemic, with a neurodegenerative illness that affects their respiratory function. It is our hope that CNM-Au8 will become another option for treating this devastating disease for many more people with ALS."  

The ENCALS measure is a composite of age, gender, bulbar or nonbulbar onset of ALS, respiratory function, genetic markers, and other clinical features. The ENCALS measure has been validated as correlating with a certain number of days of life expectancy for people with ALS. In contrast to typical trials for ALS, which have an approximate discontinuation rate of 25%, no participants in this trial discontinued, and nearly all enrolled in the open-label extension study.  

Nanocrystalline gold not only stabilizes mitochondrial function and metabolism, but also stops accumulation of TAR DNA binding protein 43 (TDP43), which is known to spread in the brains of people with ALS. Other studies of nanocrystalline gold have shown that it crosses the blood-brain barrier. Subanalyses of future studies to evaluate the potential of TDP43 as a biomarker with MR spectroscopy are also planned. 

These data were presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7 in Seattle, WA and virtually April 24-26.