'Pied Piper' Device That Lures Tumors From The Brain Awarded Breakthrough Status By FDA

Brain tumors are notoriously difficult to treat, often growing quickly and spreading through the brain. But what if we could trick the cancerous cells to proliferate in a new direction, essentially luring them out of the brain and outside the skull? Well, researchers are attempting to do just that, and their work has been awarded “ breakthrough status” by the government.

Called the Tumor Monorail, the device has been described as a “pied piper”, thanks to its ability to trick and lure cells away from a tumor, just as the Pied Piper lured rats, and then children, away from the town of Hamelin in the well-known fairy tale.

The Tumor Monorail is essentially a long, thin tube with a small reservoir at one end. The reservoir sits on top of the skull, just under the scalp, and tricks tumor cells into migrating up the tube and out of the brain where they can be removed by a surgeon. It does this by mimicking the brain’s white matter, where the tumor would normally grow. The cancerous cells spread up the tube, thinking they are growing further into the brain and expanding the tumor. Gotcha.

So far, the Tumor Monorail has only been tested successfully in rats. The researchers now need to work on testing its safety and efficacy in humans. That’s why its new breakthrough status is so important. Developing new treatments and proving they are fit for clinical use is a long, ardous process, but the FDA breakthrough initiative helps to fast-track the development and review of new treatments for serious or life-threatening illnesses.

Glioblastoma – an aggressive type of brain tumor with a poor survival rate – is one of these conditions. Innovative new ways to tackle it, like the Tumor Monorail, could have a hugely positive impact, so speeding up its development is key. Still, it’s important to note that the new allocation doesn’t mean the device has been approved for clinical use by the FDA. The researchers behind it will have to prove it's both safe and effective in people first.

“The tumor monorail device is a true game-changer in how we think about treating brain tumors,” said  a neurosurgeon in a statement. “There are many tumors that are considered inoperable due to the location of the tumor or the frailty of the patient. This device affords clinicians the ability to surgically treat these tumors with a minimal approach.”

Back in 2014, the researchers successfully managed to get their device to work in rats. The rats’ brain tumors shrank by more than 90 percent and spread more slowly. Since then, the researchers have tweaked the device, and repeatedly shown its effectiveness in rats.

“This was the first demonstration that you can engineer migration inside the body and move a tumor from point A to point B by design,” explained  one of the researcher. “It was also the first demonstration of bringing the tumor to your drug rather than your drug going into the brain and killing valuable cells.”

Five years on and the device has breakthrough status. “The most exciting part about this designation is that it gives us the opportunity to look at the FDA as a partner rather than a reviewer,” said project leader. “With direct access to the FDA reviewers, we can get more efficient, faster feedback on our experimental ideas to make sure we’re addressing all of their concerns from the very start.”

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Squirrels provide clues to new stroke treatments

Hibernating ground squirrels have provided clues to new treatments for brain damage caused by stroke. While the animals' brains experience dramatically reduced blood flow during hibernation, just like human patients after a certain type of stroke, the squirrels emerge from their extended naps suffering no ill effects.

Now, a team of scientists identified a potential drug that could grant the same resilience to the brains of ischemic stroke patients by mimicking the cellular changes that protect the brains of those animals.

"For decades scientists have been searching for an effective brain-protecting stroke therapy to no avail. If the compound identified in this study successfully reduces tissue death and improves recovery in further experiments, it could lead to new approaches for preserving brain cells after an ischemic stroke," said researcher.

Currently, the only way to minimize stroke-induced cell death is to remove the clot as soon as possible. A treatment to help brain cells survive a stroke-induced lack of oxygen and glucose could dramatically improve patient outcomes, but no such neuroprotective agents for stroke patients exist.
Recently, researchers found that a cellular process called SUMOylation goes into overdrive in a certain species of ground squirrel during hibernation. The researcher suspected this was how the animals' brains survived the reduced blood flow caused by hibernation, and subsequent experiments in cells and mice confirmed his suspicions.

SUMOylation occurs when an enzyme attaches a molecular tag called a Small Ubiquitin-like Modifier (SUMO) to a protein, altering its activity and location in the cell. Other enzymes called SUMO-specific proteases (SENPs) can then detach those tags, thereby decreasing SUMOylation.
Lead author Joshua Bernstock and his colleagues examined whether any of over 4,000 molecules from the NCATS small molecule collections could boost SUMOylation by blocking a SENP called SENP2, which would theoretically protect cells from a shortage of life-sustaining substances.
The researchers first used an automated process to examine whether the compounds prevented SENP2 from severing the connection between a tiny metal bead and an artificial SUMO protein created in the lab. This system, along with computer modeling and further tests performed both in and outside of cells, whittled the thousands of candidate molecules down to eight that could bind to SENP2 in cells and were non-toxic. Two of those - ebselen and 6-thioguanine - were then found to both boost SUMOylation in rat cells and keep them alive in the absence of oxygen and glucose.
A final experiment showed that ebselen boosted SUMOylation in the brains of healthy mice more than a control injection. 6-thioguanine was not tested because it is a chemotherapy drug with side effects that make it unsuitable as a potential stroke treatment. The researchers now plan to test whether ebselen can protect the brains of animal models of stroke.

Because SUMOylation affects a variety of molecules, researcher believes his group's approach could inspire similar attempts to treat neurological conditions by targeting pathways with wide-ranging effects. He also hopes it will prompt others to look to natural models, as researchers did with the ground squirrel.

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