Pulse 181: New Drug May Reverse Cognitive Decline

8 December 2020
Giulio Prisco
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Cognitive Decline

Scientists at UC San Francisco have found that just a few doses of an experimental drug called ISRIB can reverse age-related declines in memory and mental flexibility in laboratory mice. A study published in eLife reports rapid restoration of youthful cognitive abilities in aged mice. The change was accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.

“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,” said Professor Susanna Rosi. “We’ve seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline ... asking whether the drug could reverse symptoms of aging itself was just a logical next step.”

ISRIB (ISR InhiBitor) was discovered in 2013 in Professor Peter Walter’s lab. It works by rebooting the protein production machinery of cells damaged by “Integrated Stress Response” (ISR).

The drug has already been shown in laboratory studies to restore memory function months after traumatic brain injury. It may also reverse cognitive impairments in Down Syndrome, prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy animals.

UCSF has licensed ISRIB to Calico. Calico is a company founded by Google to research potential applications to combat aging.

“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,” said Walter. “Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time.”

Vision Restored in Old Mice

Harvard Medical School scientists have successfully restored vision in laboratory mice. They did this by reprogramming aged eye cells in the retina to recapture youthful gene function.

A research paper is published in Nature. It reports that the scientists used an adeno-associated virus (AAV) to deliver into the retinas of mice three “youth-restoring” genes that are normally switched on during embryonic development.

Besides resetting the cells’ aging clock, the scientists successfully reversed vision loss in animals with a condition mimicking human glaucoma. Glaucoma is a leading cause of blindness around the world.

According to the scientists, this represents the first demonstration that it may be possible to safely reprogram complex tissues, such as the nerve cells of the eye, to an earlier age. According to Nature News, this suggests a new approach to reversing age-related decline. When some cells are reprogrammed to a ‘younger’ state, they are better able to repair or replace damaged tissue.

Gigantic AI Leap Solves Protein Folding Problem

DeepMind is an Artificial Intelligence (AI) company and research laboratory founded in 2010 and acquired by Google in 2014. It has announced that its AI system, AlphaFold, is able to solve the protein folding problem. It can determine a protein’s 3D shape from its amino-acid sequence.

Solving the protein folding problem is very important because what a protein does largely depends on its unique 3D structure. Therefore, the ability to predict the 3D structure of a protein is expected to be a very significantly boost to drug discovery and analysis, among other things.

The CASP evaluation group stated in a press release that AlphaFold “has proved capable of determining the shape of many proteins ... to a level of accuracy comparable to that achieved with expensive and time-consuming lab experiments.”

According to experts interviewed by Nature, this is a gigantic leap that will “change everything” and a game changer for life sciences and medicine.

Designer Virus Trains Body To Fight Cancer

City of Hope scientists have developed a cancer-killing virus. It could one day improve the immune system's ability to eradicate tumors in colon cancer patients. This is reported in a study published in Molecular Cancer Therapeutics.

The new oncolytic (cancer-killing) designer virus is called CF33. It trains the immune system to target a specific cancer cell. Preclinical models show that using CF33 in combination with other therapeutic agents leads to lasting anti-tumor immunity. This means that if a similar cancer cell ever tries to regrow, the immune system will be ready and waiting to shut it down.

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