A molecular compound CLR01 dubbed "molecular tweezers," which prevents toxic proteins from aggregating or clumping together and killing brain cells in Alzheimer's disease is being developed.
Researchers at UCLA demonstrated that the compound safely crossed the blood-brain barrier, cleared the existing amyloid-beta and tau aggregates, and also proved to be protective to the neurons' synapses - another target of the disease - which allow cells to communicate with one another.
"This is the first demonstration that molecular tweezers work in a mammalian animal model," Gal Bitan, an associate professor of neurology at UCLA and the senior author of the study, said.
"Importantly, no signs of toxicity were observed in the treated mice. The efficacy and toxicity results support the mechanism of this molecular tweezer and suggest these are promising compounds for developing disease-modifying therapies for Alzheimer's disease, Parkinson's and other disorders," he said.
Bitan and his colleagues, including Aida Attar, first author of the study and a graduate student in Bitan's lab, have been working with a particular molecular tweezer called CLR01.
In collaboration with scientists at the Universita Cattolica in Rome, the researchers, working first in cell cultures, found that CLR01 effectively inhibited a process known as synaptotoxicity, in which clumps of toxic amyloid damage or destroy a neuron's synapses.
Even though synapses in transgenic mice with Alzheimer's may shut down and the mice may lose their memory, upon treatment, they form new synapses and regain their learning and memory abilities.
"For humans, unfortunately, the situation is more problematic because the neurons gradually die in Alzheimer's disease," Bitan said.
"That's why we must start treating as early as possible. The good news is that the molecular tweezers appear to have a high safety margin, so they may be suitable for prophylactic treatment starting long before the onset of the disease," he said.
The report has been published in the journal Brain.