Researchers at Yale School of Medicine have developed a compound that improves cognitive functions in Alzheimer's disease with a single dose.
In mice, the compound TC-2153 inhibits the negative effects of a protein called STtriatal-Enriched tyrosine Phosphatase (STEP), which affects learning and memory.
The findings are published in the August 5 issue of the journal PLoS Biology.
High levels of STEP proteins keep synapses in the brain from strengthening. Synaptic strengthening is a process that is required for people to turn short-term memories into long-term memories. STEP inactivates other proteins necessary for cognitive function, leading to many neuropsychiatric and neurodegenerative disorders.
By inhibiting STEP, the compound produced a reversal of deficits in several cognitive exercises that gauged the animals' ability to remember previously seen objects.
It took the collaborators five years to identify the STEP inhibitor among thousands of small molecules. The team is currently testing the TC compound in other animals with cognitive defects, including rats and non-human primates.
No treatment so far
Alzheimer's affects tens of millions of people around the world. Its cause is unknown and there are no effective treatments. While different approaches have been tried in finding a treatment in the last decade, no drugs have resulted. Cholesterol-lowering drugs and anti-inflammatory medications have been of no help.
Even the amyloid hypothesis, which suggests a build up of a protein beta amyloid in the brain leads to dementia, has not led to an approved therapy. Roche had mixed results with its drug based on this theory. It could only delay a decline in mental ability, and even that with very high doses.
A BACE inhibitor, which has been in development for more than 10 years, reduced levels of plaque forming beta amyloid. But in some clinical trials it showed side-effects on the liver.