How to Destroy the Power Source of Brain Tumor

An Israeli study has eliminated glioblastoma, the most deadly brain tumors, in mice by identifying and destroying their “power source.” The Tel Aviv University scientists behind the peer-reviewed research are now working on identifying drugs to replicate the effect in humans. They hope to find an existing drug that may work and then repurpose it, which they say could happen within two years if things go smoothly.

The method is basically to “starveglioblastoma tumors by removing their source of energy, said brain immunologist Dr. Lior Mayo, the lead author of the study. He told The Times of Israel that normally, scientists try to attack tumors directly, for example with chemotherapy. “Instead, we decided to ask if there’s anything we can change in the tumor’s environment that could harm it,” he explained.

Astrocytes are brain cells that are so called because they look like stars. Glioblastoma tumors shifts the surrounding astrocytes to an unusually active state. Mayo, and his PhD students Adi Tessler and Rita Perelroizen, wanted to know what the astrocytes do in relation to the tumor. Using genetic modification, he could produce mice with glioblastoma tumors, and then remove all astrocytes from around the tumor.

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An image from the lab of Dr. Lior Mayo showing a glioblastoma tumor in white, surrounded by astrocytes in blue

“We found that when we did this, the tumors vanished and stayed away for as long as we repressed the astrocytes,” Mayo said. “In fact, even when we stopped suppressing the astrocytes, some 85 percent of the mice stayed in remission. However, among the control group, in which all astrocytes remained, all mice died.”

In the study, published in the journal Brain, the scientists suggest “that targeting astrocyte immunometabolic signaling may be useful in treating this uniformly lethal brain tumor.”

Source: https://www.timesofisrael.com/

Toxic Fatty Acids Play a Critical Role in Brain Cell Death

Rodent studies led by researchers at NYU Grossman School of Medicine have found that cells called astrocytes, which normally nourish neurons, also release toxic fatty acids after neurons are damaged. The team suggests that this phenomenon is likely the driving factor behind most, if not all, diseases that affect brain function, as well as the natural breakdown of brain cells seen in aging.

Our findings show that the toxic fatty acids produced by astrocytes play a critical role in brain cell death and provide a promising new target for treating, and perhaps even preventing, many neurodegenerative diseases,” said Shane Liddelow, PhD, who is co-senior and corresponding author of the researchers’ published paper in Nature. In their report, which is titled, “Neurotoxic reactive astrocytes induce cell death via saturated lipids,” the team concluded. “The findings highlight the important role of the astrocyte reactivity response in CNS injury and neurodegenerative disease and the relatively unexplored role of lipids in CNS signaling.”

 

Astrocytes—star-shaped glial cells of the central nervous system (CNS)—undergo functional changes in response to CNS disease and injury, but the mechanisms that underlie these changes and their therapeutic relevance remain unclear, the authors noted. Interestingly, previous research has pointed to astrocytes as the culprits behind cell death seen in Parkinson’s disease and dementia, among other neurodegenerative diseases. “Astrocytes regulate the response of the central nervous system to disease and injury, and have been hypothesized to actively kill neurons in neurodegenerative disease,” the researchers stated. But while many experts believed that these cells release a neuron-killing molecule to clear away damaged brain cells, the identity of the toxin has remained a mystery.

The studies by Liddelow and colleagues now provide what they say is the first evidence that tissue damage prompts astrocytes to produce two kinds of fats, long-chain saturated free fatty acids and phosphatidylcholines. These fats then trigger cell death in damaged neurons. For their investigation, researchers analyzed the molecules released by astrocytes collected from rodents. “Previous evidence suggested that the toxic activity of reactive astrocytes is mediated by a secreted protein, so we first sought to identify the toxic agent by protein mass spectrometry of reactive versus control astrocyte conditioned medium (ACM),” they wrote.

Source: https://www.genengnews.com/

Algorithms Boost Cell Therapy

Cellular therapy is a powerful strategy to produce patient-specific, personalised cells to treat many diseases, including heart disease and neurological disorders. But a major challenge for cell therapy applications is keeping cells alive and well in the lab.

That may soon change as researchers at Duke-NUS Medical School, Singapore, and Monash University, Australia, have devised an algorithm that can predict what molecules are needed to keep cells healthy in laboratory cultures. They developed a computational approach called EpiMogrify, that can predict the molecules needed to signal stem cells to change into specific tissue cells, which can help accelerate treatments that require growing patient cells in the lab.

Computational biology is rapidly becoming a key enabler in cell therapy, providing a way to short-circuit otherwise expensive and time-consuming discovery approaches with cleverly designed algorithms,” said Assistant Professor Owen Rackham, a computational biologist at Duke-NUS, and a senior and corresponding author of the study, published today in the journal Cell Systems.

In the laboratory, cells are often grown and maintained in cell cultures, formed of a substance, called a medium, which contains nutrients and other molecules. It has been an ongoing challenge to identify the necessary molecules to maintain high-quality cells in culture, as well as finding molecules that can induce stem cells to convert to other cell types.

The research team developed a computer model called EpiMogrify that successfully identified molecules to add to cell culture media to maintain healthy nerve cells, called astrocytes, and heart cells, called cardiomyocytes. They also used their model to successfully predict molecules that trigger stem cells to turn into astrocytes and cardiomyocytes. “Research at Duke-NUS is paving the road for cell therapies and regenerative medicine to enter the clinic in Singapore and worldwide; this study leverages our expertise in computational and systems biology to facilitate the good manufacturing practice (GMP) production of high-quality cells for these much needed therapeutic applications,” said Associate Professor Enrico Petretto, who leads the Systems Genetics group at Duke-NUS, and is a senior and corresponding author of the study.

Source: https://www.duke-nus.edu.sg/