Novel Drug Reverses Age-Related Cognitive Impairment

A few doses of a new drug ISRIB (Integrated Stress Response Inhibitor) can reverse age-related decline in memory and mental flexibility in mice.

According to the laboratory studies, the drug was able to reverse cognitive impairments in Down Syndrome, restore memory functions after traumatic brain injury (TBI), increase cognition in healthy animals, prevent hearing loss due to noise, and fight certain types of prostate cancer.

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Cognitively normal adults exhibiting atrophy of their temporal lobe or damage to blood vessels in the brain are more likely to develop Alzheimer’s disease.

‘Chronic ISR activation is seen in various neurological conditions that result in blockage of cellular protein production. Few doses of ISRIB drug can reverse this blockage. No side effects were seen with the use of this drug.’
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The research conducted by scientists at UC San Francisco was published in the journal eLife

Improvements in brain function in aged mice were seen with rapid restoration of youthful cognitive abilities and refresh brain and immune cells.

Susanna Rosi, PhD, professor in the department of Neurological Surgery and also Physical Therapy and Rehabilitation Science said, “ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological “blockage” rather than more permanent degradation”

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Peter Walter, PhD, professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator said, “The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress. Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time.”

In normal conditions, ISR detects problems with production of protein in cells. This can be a sign of viral infection or mutations in genes that promote cancer. ISR responds by stopping the protein synthesis which is important for removing cells that malfunction. Walter and his colleagues found that if these problems are identified in brain tissues, it can lead to serious issues as the cells lose their ability to perform normal activities.

Test your Knowledge on Brain Injury
Injury to the head or brain can have a short-term as well as long-term effects. Trauma to the brain is common in young adults, as well as in the elderly due to falls. Besides trauma, other conditions like reduced oxygen supply to the brain or the presence of toxins can also injure the brain. Test your knowledge on brain injury by taking this quiz.

Chronic ISR activation is seen in patients after traumatic brain injury which results in persistent cognitive and behavioral problems. The researchers showed that treatment with ISRIB in mice can reset ISR and restore normal brain function almost overnight.

The studies have showed that ISR is accumulated in the neurons throughout the brains of animals who have suffered traumatic brain injury acting as brakes. ISRIB releases these brakes and restores normal function. Recent studies have showed that in animals with repetitive brain injury, like concussions in athletes, ISRIB was able to reverse the increased risk-taking behavior seen due to damage to the self-control circuits in the frontal cortex.

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No serious side effects were seen with this drug as only a few doses of the drug are required.

Conditions in which ISRIB can be used include-

Alzheimer’s disease
Amyotrophic Lateral Sclerosis (ALS)
Parkinson’s disease
Traumatic brain injury
Multiple Sclerosis
Down Syndrome
Age-related Cognitive Decline
Prion disease
Vanishing White matter Disorder
Frontotemporal Dementia

Source-Medindia