Mice work! New drug could restore memory after traumatic brain injury
20th July 2017
By Elliot Miller
An experimental drug called ISRIB has been found to reverse cognitive impairments in brain injured mice. This ground-breaking research, published in the Proceedings of the National Academy of Sciences, offers hope of a potential treatment for traumatic brain injury (TBI) patients.
Researchers from the University of California, San Francisco (UCSF), first discovered the memory-enhancing effects of ISRIB back in 2013. The lab of UCSF biochemist Peter Walter found the compound to boost the memory of healthy mice, and so its effect in brain injured mice was tested.
Mice were dealt blows to the brain under anaesthesia and the effect of ISRIB was studied in two different models of TBI. The first model was for focal injuries, which occur in a specific region of the brain following a focused blow to the head, similar to when someone has a stroke. Mice were trained to swim through a water maze 4 weeks after a surgical focal injury, and there was an improvement in healthy mice but not brain injured ones. However, when ISRIB was given for 3 consecutive days, they found that brain injured mice were able to solve the maze as quick as healthy mice.
The second model was for closed head injuries, similar to a concussion after a heavy fall. Two weeks after a concussive injury, mice had to scurry around a tabletop and find an escape tunnel among 40 holes, in a room full of bright lights and loud noise. At first, only healthy mice improved at the task. Yet when ISRIB was administered for a course of 4 days to brain injured mice, their performed was similar to healthy mice.
These results open up the possibility of reversing memory impairments for TBI patients, with a potential new avenue for treating Alzheimer’s and other forms of dementia. But as mouse brains are different from human brains, caution is needed when interpreting the findings. Researchers at biotechnology company Calico are attempting to identify the specific mechanisms of ISRIB’s action, to determine whether the results will translate to humans. It has been hypothesized that ISRIB allows normal protein synthesis – otherwise stopped by the integrated stress response – enabling the strengthening of synaptic connections that underlie learning and memory formation.
There are reasons to be optimistic though, as ISRIB was found to be an effective treatment weeks after injury, contrary to research which claims therapy to be ineffective in the chronic period of TBI. The next stage is to test whether the drug is safe for humans, with potentially huge implications for restoring cognitive abilities following TBI in the future.
The full article can be read here: http://www.pnas.org/content/early/2017/07/05/1707661114.full.pdf