Penn State scientists find new target for Alzheimer’s therapy
LONDON — A drug to prevent the memory loss associated with Alzheimer’s disease is a step closer after scientists discovered why people with dementia cannot form new memories.
It was previously thought that Alzheimer’s was primarily caused by the buildup of plaques in the brain that stop neurons from firing. But drugs to clear the plaques have so far failed to bring any improvement to sufferers.
Many scientists believe that the plaques trigger a “cascade effect” of other symptoms meaning that by the time they are spotted it is already too late.
Researchers at Penn State University have discovered that the plaques might be triggering overproduction of a chemical known as GABA neurotransmitter that causes memory loss by preventing a key part of the brain from functioning. They believe a drug that deactivates the chemical could halt memory loss in sufferers.
“Billions of dollars were invested in years of research leading up to the clinical trials of those ( plaque- clearing) Alzheimer’s drugs, but they failed the test after they unexpectedly worsened the patients’ symptoms,” said Gong Chen, a biologist who led the work at Penn State. “The research behind those drugs had targeted the long- recognized feature of Alzheimer’s brains: the sticky buildup of the amyloid protein known as plaques, which can cause neurons in the brain to die.
“The research of our lab, and others, now has focused on finding new drug targets and on developing new approaches for diagnosing and treating Alzheimer’s disease.”
Chen’s team found that in Alzheimer’s sufferers, GABA neurotransmitter levels were dramatically increased in deformed brain cells. Those deformed cells were found in an area of the brain that is critical for learning and memory.
The team found that, in mice with excess GABA neurotransmitter, neurons were not firing like they should when the mouse was learning something new or remembering something learned. “We recently discovered an abnormally high concentration of one inhibitory neurotransmitter in the brains of deceased Alzheimer’s patients,” Chen said. “After we inhibited the ( chemical) in the brains of the mice, we found that they showed better memory capability.
“We are very excited and encouraged by this result, because it might explain why previous clinical trials failed by targeting amyloid plaques alone,” he said.
“An ultimate successful therapy may be a cocktail of compounds acting on several drug targets simultaneously.”