Medicosnext
A recent study has demonstrated that an experimental drug named ISRIB (integrated stress response inhibitor) rapidly restored youthful cognitive abilities in aged mice. The researchers said that ISRIB’s extremely rapid effects showed that an important component of age-related cognitive loss could be caused by reversible physiological “blockage”, rather than more permanent degradation.
Normally, the ISR (integrated stress response) detects problems with protein production in a cell and responds by stopping the cell’s protein-synthesis machinery. ISRIB, which was discovered in Walter’s lab at UCSF in 2013, works by rebooting this machinery. In laboratory studies, ISRIB has shown to restore memory function months after traumatic brain surgery (TBI), reverse cognitive impairments in Down syndrome, prevent noise-related hearing loss, fight some types of prostate cancer, and even improve cognitive abilities in healthy animals.
In the new study, researchers trained aged animals to escape from a watery maze. The animals who received small daily doses of ISRIB during the three-day training process accomplished the task much better than animals of the same age who didn’t receive the drug. To test how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily. The mice who had received brief ISRIB treatment still performed at youthful levels, while untreated mice continued to struggle.
The researchers are continuing the study to understand how exactly the ISR disrupts cognition in aging and how long ISRIB’s cognitive benefits could last. Interestingly, although they expected some serious side effects because they were interfering with a critical cellular safety mechanism, none have been so far.
Reference: UCSF, December 1, 2020,
