Experimental Drug May Normalize Brain Function in Alzheimer's Disease
BACE inhibitors observed to reduce amyloid production and accumulation in the brain.
Since amyloid beta is believed to be a major player in Alzheimer’s disease, compounds that reduce production of the protein, such as BACE inhibitors, have become a promising new treatment strategy.
A study published by Proceedings of the National Academy of Sciences revealed that BACE inhibitors reduce the amount of amyloid beta in the brain and can restore normal nerve cell function. These actions were found to improve memory performance, according to the study.
Approximately 50 million individuals around the world have dementia. The condition is currently incurable and the underlying cause is unclear. Specifically, in Alzheimer’s disease, amyloid beta aggregates and damages nerve cells, which results in memory dysfunction.
Cells affected by Alzheimer’s disease become hyperactive and send false signals to nearby cells. Additionally, certain brain waves involved with memory formation spin out of control.
"A successful treatment must take effect as early in the course of the disease as possible. In our experiments, we have therefore blocked the enzyme beta secretase BACE, which produces amyloid beta," said researcher Marc Aurel Busche, MD, PhD.
In the study, the authors explored the efficacy of a compound that blocks beta secretase in mouse models of Alzheimer’s disease. The mice were fed the drug for up to 8 weeks and then underwent imaging to observe their nerve cells in the brain.
Since the production of beta secretase was inhibited, the authors found that the mice had less amyloid beta in their brains.
Surprisingly, the brain function appeared normalized after treatment with the BACE inhibitor, according to the study. The authors discovered that there were fewer hyperactive nerve cells and the brain wave patterns resembled those in healthy animals.
Additionally, mice treated with the BACE inhibitor had improved memory, as they were able to locate a target in a water-filled maze with speed similar to healthy controls, according to the study.
"What really impressed and amazed us was the reversibility of the symptoms. Before the treatment, the mice had a marked clinical picture with amyloid beta plaques in their brain. Nevertheless, the substance was able to restore important brain functions and abilities," said lead author Aylin Keskin. “Moreover, the researchers' study showed yet another benefit: "We were also able to demonstrate which neural deficits really are caused by amyloid beta. That was not fully understood with regard to hyperactive nerve cells, for example.”
The authors are currently planning to conduct a large clinical trial in more than 1000 patients to determine the safety and efficacy of a modified version of the BACE inhibitor.
"Needless to say, we very much hope that the promising discoveries in the animal model will translate to humans," Dr Busche concluded.