Restoring memory

15 February 2021

Improvements in the memory of mice could usher in a new treatment for degenerative brain conditions.

Researchers from the University of California, San Francisco (UCSF), in the US, have found that a small molecule which inhibits the integrated stress response (ISR) was able to improve the working memory of elderly mice. Three injections of the ISR inhibitor were enough to reset the performance of mice aged 19 months, turning the clock back more than 12 months.

Describing the discovery as ‘revolutionary’, UCSF neuroscientist Susanna Rosi said ‘It suggests that the brain has the capability to recover even in an ageing brain.’ The researchers also said that the study indicated the ISR inhibitor can restore communication between neurons in the hippocampus, a critical region of the brain involved in storing memories.

The ISR is a short term protective measure that stops proteins being made. It is triggered by infections or build-up of aberrant proteins, as can happen in diseases such as Alzheimer’s. The main therapeutic strategy for Alzheimer’s disease has been to clear clumps of amyloid protein from the brain, but their removal did not restore cognition or prevent decline. The new study highlights a different strategy and if shown to work could be used to treat a spectrum of neurodegenerative diseases, some forms of traumatic brain injury and possibly less severe, age-associated memory loss.

The molecule is licensed to Calico Life Sciences, a company owned by Google. Safety and efficacy studies are still required before it can be advanced to clinical trials. But the researchers say that the data showing the compound can cross the blood-brain barrier and that it has little or no toxicity effects, along with the impressive physiological effects on the brain in multiple mouse models, suggests that clinical trials may be just a few years away.

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