Copper compound improves Alzheimer’s markers in lab study
Monash researchers say Cu(ATSM) reduced amyloid-beta and improved spatial memory in an Alzheimer’s disease model.
By Priya Raghavan · Science Reporter
3 min read
A copper-based drug candidate improved the brain’s clearance of amyloid-beta and boosted memory measures in laboratory Alzheimer’s disease research, according to Monash University. The findings matter because the compound, Cu(ATSM), has already been tested in people for other neurological conditions, which researchers say could support faster evaluation for Alzheimer’s disease.
Monash University said the study, published in ACS Chemical Neuroscience, focused on a faulty waste-removal process at the blood-brain barrier. The research team reported that treatment with Cu(ATSM) increased levels of P-glycoprotein, or P-gp, transport pumps that help move amyloid-beta out of the brain and into the bloodstream.
Alzheimer’s disease is linked to the buildup of amyloid-beta, a toxic protein that accumulates in the brain, according to Monash University. Under normal conditions, P-gp pumps at the blood-brain barrier help remove these proteins, but the university said the pumps are less effective in Alzheimer’s disease.
Dr. Jae Pyun, lead author and a researcher in the Drug Delivery, Disposition and Dynamics theme at the Monash Institute of Pharmaceutical Sciences, said the study connected repair of blood-brain barrier function with lower toxic protein levels and better cognition in an Alzheimer’s model.
According to Pyun, Cu(ATSM) raised the abundance of P-gp clearance pumps by 24.1%. Over 56 days, the treatment reduced toxic amyloid-beta by 42% and improved spatial learning by nearly 44%, he said.
A drug candidate with prior clinical testing
Professor Joseph Nicolazzo, senior author and director of the Centre for Drug Candidate Optimisation at the Monash Institute of Pharmaceutical Sciences, said Cu(ATSM) has anti-inflammatory and neuroprotective properties. He said the compound has already reached clinical testing for Parkinson’s disease and amyotrophic lateral sclerosis, also known as ALS.
Nicolazzo said that record of prior safety testing could make it easier to move the compound into human studies for Alzheimer’s disease. He also said the preclinical results support testing the drug in people with early symptomatic Alzheimer’s disease because lowering amyloid burden has been clinically shown to improve functional outcomes.
The findings do not establish that Cu(ATSM) treats Alzheimer’s disease in humans. Monash University described the results as laboratory findings and said further work is needed to confirm how the treatment moves amyloid-beta out of the brain after blood-brain barrier function improves.
Researchers examine other possible pathways
The Monash team said Cu(ATSM) may do more than restore P-gp pump activity. Researchers suspect it could also affect microglia, the brain’s immune cells, by helping them consume and break down amyloid plaques.
Future studies will look at the pathways that allow amyloid-beta to pass from the brain into the bloodstream, according to Monash University. The researchers said the work supports further study of biometal-based treatments for blood vessel dysfunction and memory loss linked to Alzheimer’s disease.
The study was led by Pyun and included co-authors Pranav Runwal, Oliver Fuller, Casey Egan, Professor Mark Febbraio, Associate Professor Jennifer Short and Nicolazzo from the Monash Institute of Pharmaceutical Sciences. Monash University said other authors included Dr. Asif Noor, Celeste Mawal, Professor Paul Donnelly and Professor Ashley Bush from the University of Melbourne.
Monash University said dementia has recently overtaken coronary heart disease as the leading cause of death in Australia. Researchers cited rising dementia deaths and aging populations as reasons for continued work on treatments that may slow or prevent cognitive decline.
This story draws on original reporting from ScienceDaily.