Researchers at the University of California San Diego has come up with a new mechanism to screen Alzheimer’s. They analyzed disease mechanisms in human neurons to determine the cause of the low success rate of drugs used in Alzheimer’s treatment.
The research funded by US National Science Foundation is said to be groundbreaking in the treatment of Alzheimer’s. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association published the findings.
Senior author Shankar Subramaniam noted that present treatments for Alzheimer’s were developed to target amyloid plaques, long thought to be the primary cause of neuron death and the onset of the debilitating condition. “But this approach has not led to a cure or improved dementia in patients,” he said.
Other disease mechanisms, or endotypes, are affected, including the degradation of neurons, neuron gene suppression and synaptic connection loss. The screening process examines a wider range of endotypes, a release said. “This is a new test for measuring whether an Alzheimer’s drug works,” said Subramaniam. “When drugs interact with human neurons, what endotypes do the drugs fix, and what endotypes do they not fix in the process? This method screens drugs on actual patient cells. The power of this is that you can do precision medicine and have a good model system to study Alzheimer’s.”
The researchers screened two experimental Alzheimer’s drugs designed to reduce or prevent amyloid plaque growth and found that the drugs were only partially effective.
“Now we have a prescription for what endotypes to target during drug screening,’ said Subramaniam. “What we are seeing is that fixing amyloid plaque formation does not reverse the disease. Once neurons de-differentiate into nonneurons, they lose their synaptic connections, which leads to loss of memory and cognition and as a consequence, dementia.’
The researchers plan to test the drug screening method on synthetic tissue modeled after the human brain and will continue to develop potential Alzheimer’s therapeutics. “We want to take this a step further to screen drugs on more realistic tissues, not just neurons in a dish,” said Subramaniam.