The brain is one of the most vital yet delicate organs in the human body and, as a result, brain injuries are often severe and difficult to treat. Traumatic Brain Injury (TBI) is the most common and often irremediable of these injuries. It occurs when someone suffers a severe bump or blow to the head from an external force which disrupts the normal function of the brain. The effects range in severity and may include cognitive decline and memory loss. Affecting approximately 54-60 million people worldwide and being recognised as the leading cause of disability in children and young adults, medical scientists have long been searching for a cure and, in 2017, it seems they found a drug that could be just that.
ISRIB (Integrated Stress Response Inhibitor) is a synthetic drug that was first discovered in 2013 and was used to improve the memory of healthy mice. However, in 2017, Peter Walter and Susanna Rosi of the University of California, San Francisco found that it could also be used to treat and, in fact, reverse the effects of brain trauma in them as well. It works by blocking a part of a protective cellular system called the Integrated Stress Response (ISR). When cells are injured or diseased, ISR slows down the process through which genetic instructions encoded in DNA are translated into functional proteins. Thus, as the name suggests, ISRIB inhibits the ISR and allows the cells to override it. The effects of ISRIB in mice were long term as, after only a few administrations of the drug, it was observed that a process known as long-term potentiation, (the continuous strengthening of synapses based on patterns of recent activity) occurred due to the inhibition of ISR.
To conduct the experiment, Walter and Rosi first used mechanical pistols on the mice’s surgically exposed brains to inflict contusive injury (of the severity such as that likely caused by a motor accident). Four weeks later, the mice were taught to swim through a maze while being given cues to remember the location of hidden resting platforms. As could be expected, the healthy mice improved over time but the injured mice did not. However, after being given ISRIB for three days in a row, they began to improve at the same rate as the healthy mice and, a week later, could solve the maze just as quickly. Shocked by the results, the team repeated the experiment with different TBIs and tasks that the mice were given to complete to confirm the reliability of the drug and found that ISRIB was effective in all cases.
Understandably, much more research needs to be conducted on ISRIB before clinical trials commence and it is not unlikely likely that the drug may not be as effective on humans as it has been on mice, as is often the case.
However, the potential that it holds is incredible. Because of TBIs, thousands of people suffer with no hope of reverting to the way their life was prior to the injury. But, with ISRIB, as neuroscientist Carlos Borlongan said, they “[are offered] a glimmer of hope” to potentially even make a full recovery.
Elisa Karaim Year 11
Edited by Mariam Malak Year 11