A step forward in treating Alzheimer’s

Researchers have known that STriatal-Enriched protein tyrosine Phosphatase (STEP), an enzyme key to regulating learning and memory in the brain, also plays a role in diseases marked by cognitive defects: in people with Alzheimer’s, Parkinson’s, schizophrenia, and other diseases, high levels of STEP disrupt the normal development and strengthening of the brain’s neurons.

Now, a team led by Paul J. Lombroso, M.D., the Elizabeth Mears and House Jameson Professor in the Child Study Center, has developed a drug that inhibits STEP’s negative effects.

For five years, Lombroso’s team screened more than 150,000 compounds in search of one that blocks STEP activity. Eventually they landed on a drug called TC-2153. In the Aug. 5 issue of PLoS Biology, Lombroso’s team reported that TC-2153 reversed memory deficits in mice with an animal version of Alzheimer’s disease. By entering the brain and effectively binding to and inhibiting STEP, the drug prevented the protein from disrupting synaptic activity in neurons.

The researchers are now testing the compound in other animals with cognitive defects. “Successful results will bring us a step closer to testing a drug that improves cognition in humans,” says Lombroso, also professor of neurobiology and psychiatry.