An experimental drug appeared to restore normal memory and cognition function in mice, according to researchers at the University of California, San Francisco (UCSF).
Known as ISRIB, the drug is an integrated stress response inhibitor. Earlier laboratories suggested the drug holds promise in treating disorders ranging from traumatic brain injury to noise-related hearing loss to prostate cancer.
The scientists noted in the study published in eLife that normal aging activates the integrated stress response, contributing to changes in brain function and memory. In particular, aging leads to diminished protein synthesis within the brain related to protein folding defects. While ISR plays a role in curbing abnormal cellular function in the short-term, it can contribute to age-related disorders when permanently activated.
The study showed that ISRIB reversed ISR activation in the brain, stemming spatial memory deficits and boosting working memory in aging mice. ISRIB also spurred the rejuvenation of brain and immune cells.
The effects of the drug were rapid, occurring after a few doses. “ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological “blockage” rather than more permanent degradation,” explained Susanna Rosi, a UCSF professor in prepared remarks.
The researchers tested mice’s cognitive abilities by watching them escape from a modified Barnes maze and monitoring their neuronal activity. Older mice that received small doses of ISRIB in the course of a three-day training period performed as well as younger mice and had improved function in the hippocampus. Their cognitive ability persisted three weeks after treatment.
In 2013, UCSF researchers announced the ISRIB molecule improved memory performance in normal mice.
A 2016 STAT profile on Walter noted that some scientists were skeptical of the molecule, citing its potential to interfere with typical cellular performance. ISRIB could be years or even decades away from human testing, according to those researchers.
The researchers plan on investigating ISRIB’s potential in treating other disorders such as Alzheimer’s disease and diabetes.
Filed Under: Drug Discovery, Neurological Disease