A study by Yale University has found a Silent Allosteric Modulation (SAM) drug named BMS-984923to be capable of recovering neuronal synapse losses in mice models for Alzheimer’s disease (AD), creating hope for human dementia patients affected by AD.
Synapses are the gaps or connections between neurons, working as connection points between neurons.
Most neurons communicate by passing chemical or electrical messages from the end of the nerve past the synapse to the following neuron, forming neural networks that allow neurons across the brain and body to communicate.
Therefore, synapse loss is seen as a sign of cognitive and memory decline, due to the loss of communications of neurons across the brain.
However, prior to visible symptoms of decline in memory and behavior, a hallmark sign of AD is an accumulation of an abnormal protein called amyloid between neurons, forming plaques, often taking decades before visible signs of memory and behavioral deficits appear.
Components of amyloid and prion, a type of protein common to the brain can drive synapse and memory loss by interacting with a specific glutamate receptor on neurons.
Whilst this prevented amyloid and other protein interactions from inducing further loss of synapse, inhibition of this interaction did not reduce the plaques forming in the brain.
The drug was also observed to recover lost synapses in both Alzheimer’s and dementia mice models.
Mice bred to old age with mimicked loss of synaptic densities seen in dementia had drastic improvements in densities following exposure, with the effects of the improvements remaining up to 1 month after the drug was administered.
The team also mimicked early-onset AD inherited through breeding mutated mice and observed that exposure to the drug resulted in a 17 percent increase in synapse density.
Rather than recovering lost synapses, the authors found that the drug formed and stabilized new junctions by improving growth of branches in neurons, forming more connections.
However, researchers speculate that the improvement growth is a signal the drug could drive rebalance of growth and loss processes rather than simply boost synapse growth alone, as the normal mice saw no significant growth in synapses after administration.
“SAM treatment was shown to have a disease-modifying benefit,” wrote the authors, suggesting future treatments of SAM to work in synergism with other plaque-controlling treatments.
Testing for the drug in humans has begun in early-stage clinical trials.
The study is published in Science Translational Medicine, an online, peer-reviewed journal.
