Potentially groundbreaking drug reverses Alzheimer’s disease in mice, NYU researchers say

NEW YORK — Alzheimer’s disease is the most common form of dementia and impacts the lives of millions of Americans. The memory-erasing condition can worsen to the point of making it hard for a patient to even hold a coherent conversation. There is no cure for the disease, and doctors have long sought ways to slow its progression. Now, researchers have created a drug that successfully reverses Alzheimer’s in mice. It fuels the production of memory-boosting proteins, offering hope of a cure.

The potentially groundbreaking compound also strengthens connections, or synapses, between neurons, improving communication.

Lead author Dr Mauricio Martins-Oliveira, of New York University (NYU), said it opens the door to treating the causes of dementia. “This work is the first to show reversing impaired protein synthesis in brains afflicted by Alzheimer’s through a pharmacological approach is not only feasible, but also effective,” he explains in a statement.

What’s more, it even worked in advanced stages of the disease, rescuing the activity of cells needed for memory formation.

One of reasons trials of new medications have failed to date is they are prescribed to patients once the condition has already taken hold. In memory tests, such as navigating a maze, the brainpower of older mice was restored after they were injected with ISRIB (ISR InhiBitor). The experimental drug works by correcting a chemical pathway called the integrated stress response (ISR).

“The synthesis of new proteins in the brain is essential for proper neuronal function and, notably, for memory consolidation,” says co-senior author  Sergio Ferreira, a professor at the Institute of Biophysics at Brazil’s Federal University of Rio de Janeiro. “We and others have previously shown impairments in brain protein synthesis contribute memory deficits in Alzheimer’s model mice, and the brains of patients exhibit clear signs of impaired protein synthesis. We thus asked ourselves whether rescuing brain protein synthesis might be an approach to improve memory function in Alzheimer’s.”

‘Step forward’ in a viable, effective treatment of Alzheimer’s disease

The drug stimulates protein production by specifically targeting the translation of genetic codes. Previously, the same team had shown this is impaired in Alzheimer’s, especially in the brain’s hippocampus that controls memory. It led them to suspect ISRIB would re-establish cognitive functions.

Synaptic plasticity, the ability of the brain to change in order to learn, and memory returned to the lab rodents. The drug also brought back the hippocampal functions and mental abilities of mice with fully developed Alzheimer’s-like afflictions, This was after the disease at its most extreme form was mimicked in the animals.

Similarly, the results demonstrated ISRIB regenerated synapses in the hippocampus as well as memory. The researchers say repairing protein production with ISRIB is a “promising avenue” in combating Alzheimer’s. “Our findings show jump-starting protein synthesis in the brain can revive lost cognitive functions,” adds co-senior author Eric Klann, a professor in NYU’s Center for Neural Science. “We hope this work can serve as a step forward in treating this devastating disease.”

Currently, Alzheimer’s treatments focus on the reduction of rogue proteins called beta amyloid and tau that clump together destroying neurons. The study, published in the journal Science Signaling, provides an alternative potential target for reviving the brain.

What is ISRIB?

ISRIB was created by Peter Walter, a professor at the University of California, San Francisco, in 2013. It reboots cells’ protein production machinery after it gets throttled by responses to stress. Laboratory studies have suggested it can improve memory after traumatic brain injury (TBI) and reverse cognitive impairments in Down Syndrome. It may also prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy individuals.

The ISR normally detects problems with protein production, a potential sign of viral infection or cancer-promoting gene mutations. It responds by putting the brakes on cells’ synthesis. This safety mechanism is critical for weeding out misbehaving cells.

But if stuck in the ‘on’ position in a tissue like the brain, it can lead to serious problems. Cells lose the ability to perform their normal activities, Walter and colleagues have found.

In 2014, the Centers for Disease Control and Prevention estimated as many as 5 million Americans have Alzheimer’s disease. They predict that number will balloon to 14 million by 2060.

SWNS writer Mark Waghorn contributed to this report.