Towards Clinical Trials for ISRIB
ISRIB has for some years been under investigation as a way to reduce the impact of neurodegeneration and improve cognitive function. It is one of a number of small molecule approaches to upregulate forms of cellular housekeeping, the unfolded protein response in this case. More cellular maintenance in principle means a lower burden of molecular damage and cellular dysfunction at any given time. Since most of these maintenance processes appear to decline in efficacy with age, improvement is a compensatory strategy that might help. In many cases exercise produces more impressive effects than the present state of the art in pharmacology, however. We shall see how ISRIB does in humans, but the mouse data is interesting.
ISRIB has restored memory formation in mice months after traumatic brain injuries and shown potential in treating neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). It also seems to reduce age-related cognitive decline. Researchers believe that the reason the molecule can do so much is that it plays an essential role in how the brain handles stress from physical injuries or neurological diseases. Under siege from such problems, the brain, in essence, shuts down cognitive functions like memory formation to protect itself. The new molecule reverses that.
Will ISRIB work to reverse cognitive decline in people? We still don't know. So far most of the work has been done in mice or human cells in a petri dish. But we will soon know more: in 2015 the molecule was licensed by Calico Labs, the Silicon Valley biotech established by the founders of Google to find drugs based on the biology of aging. It aims to transform the molecule into a treatment for a wide array of disorders, including ALS and Parkinson's disease, as well as the damage from traumatic brain injury. In 2021, Calico announced that human safety trials had begun on the first drug candidate for neurodegenerative diseases it had developed based on ISRIB, and that a study in ALS patients was slated to begin later in the year.