Affecting 44 million individuals globally, Alzheimer’s disease (AD) is a form of dementia characterized by loss of brain cells, inflammation and vasculopathy. A defining feature of AD is the presence of a protein known as amyloid beta (Aβ) that clumps up into amyloid plaques.
These plaques affect memory and cognitive functions and progressive accumulation of the protein is toxic leading to neurodegeneration. Past clinical studies have focused on decreasing the levels of Aβ, through possible developments of Aβ vaccine-based therapies. However, current approved therapeutics do not work to alter the pathology of AD in it patients.
Now, recent research published by researchers in the University of Alberta, shows that a short sequence peptide fragment known as AC253 provides neuroprotective properties against Aβ toxicity in model mice. When a variant of this fragment is administered systemically, it was shown to improve spatial memory and learning in mice as well as attenuating plaque accumulation and inflammation in the brain. Future drug development based on this peptide will advance how to tackle AD disease progression.
“This has been 15, 20 years of painstaking and incremental work,” says University of Alberta Distinguished University Professor and neurologist Jack Jhamandas. “And it's like building a house: you put one brick down, then you put another brick on top of that, and pretty soon you have a foundation and then you have a house.
Learn more about current therapeutic advances in Alzheimer’s Disease (AD):
“In the mice that received the drugs, we found less amyloid plaque buildup and a reduction in brain inflammation,” said Jhamandas, who is also a member of the Neuroscience and Mental Health Institute. “So this was very interesting and exciting because it showed us that not only was memory being improved in the mice, but signs of brain pathology in Alzheimer’s disease were also greatly improved. That was a bit of a surprise for us.”
Via Folio.ca: U of A neurologist Jack Jhamandas led a team that found a new treatment significantly improved memory in mice with Alzheimer's disease. The researchers are now developing a drug that could eventually be used to treat human patients. (Photo: Jordan Carson)
The research brings a new outlook on peptide-based therapeutics and their potential in disease pathology. The study uses cell-based peptide library screening to demonstrate how peptide fragments based on AC253 sequence work to improve pharmacokinetics. Drugs based on this sequence have the potential to cross the blood-brain barrier in the central nervous system, and reverse spatial memory deficits in transgenic AD mice.
Findings of the study were published Scientific Reports by Nature Research.
Source: Science Daily