The publication, led by Morteza Mahmoudi, associate professor at the department of radiology and precision health program at Michigan State University, fully characterized the proteins from human blood plasma that form the protein corona of the gold nanocrystals of CNM-Au8.
“The protein corona of CNM-Au8 gold nanocrystals, tailored for brain delivery applications, exhibits a unique composition, notably enriched with critical apolipoproteins such as apolipoprotein E. This composition enhances the nanocrystals' ability to traverse the blood-brain barrier,” Mahmoudi said.
“Simultaneously, the depletion of opsonin-based proteins in the corona extends their circulation time in the blood, as observed clinically. Our research underlines that these engineered gold nanocrystals, designed with specific structures and without surfactants, can form a distinct protein corona that facilitates access to brain tissue."
The protein corona attracted by CNM-Au8 nanocrystals also prevents aggregation upon entering the bloodstream, enabling the drug’s longevity in circulation without provoking an inflammatory response
As a result, CNM-Au8's ability to cross the blood-brain barrier allows it to successfully reach neurons in the central nervous system.
In addition, previous phase 2 trials have shown that CNM-Au8 favourably affects levels of brain metabolites in people with multiple sclerosis and Parkinson’s disease.
“Our extensive nonclinical toxicity and clinical pharmacokinetics studies have demonstrated that CNM-Au8 reaches steady state levels in blood without any serious adverse effects, such as inflammatory or immunomodulatory issues, identified as related to CNM-Au8 treatment,” said Michael Hotchkin, chief development officer at Clene.
“Across 500+ years of patient exposure in multiple Phase 2 clinical trials and expanded access programs, CNM-Au8 treatment has been shown to be safe and well-tolerated. These prior clinical results are further enriched by the findings from this work explaining how the protein corona forms around CNM-Au8 once in the bloodstream, and how this corona preferentially aids access through the blood-brain barrier to support CNM-Au8’s activity in the brain.”
This new data, published in the journal ACS Pharmacology & Translational Science, shows that ‘the corona composition of the CNM-Au8 nanocrystals contribute further favourable drug properties to our neuroprotective agent, consistent preclinical and clinical studies’ added Mark Mortenson, chief science officer at Clene.
A phase 3 registrational clinical trial of CNM-Au8 for the treatment of the progressive neurodegenerative disease, amyotrophic lateral sclerosis, is now set to launch in 2024.