Study finds potential treatment for deadly brain cancer that killed Ted Kennedy

Glioblastoma mutliforme (GBM) is one of the deadliest types of brain cancer, killing approximately 13,000 people every year – including Sen. Ted Kennedy in 2009. But now, researchers from Northwestern University have demonstrated a way to potentially treat this incurable, aggressive disease, by switching off a critical gene associated with the cancer.

According to study author, Alexander H. Stegh, an assistant professor in the department of neurology at the Northwestern University Feinberg School of Medicine, few treatment options are currently available to the estimated 16,000 people diagnosed with GBM in the United States every year. In fact, most patients succumb to the disease within 16 to 18 months of their diagnosis.

“The best we can do for GBM patients right now is to resect the tumor and then give them extended chemotherapy and radiation,” Stegh told “…The combined regimen increases survival by three to four months only, so these are clearly numbers that convey the highly lethal nature of this disease.”

Stegh’s laboratory has spent years studying the genetic underpinnings of GBM, in order to better understand the disease. In 2007, they discovered that more than 90 percent of GBM patients had an overexpression of a gene called Bcl2Like12 in their tumor cells. Additionally, the researchers noticed that patients with especially high levels of this gene expression also had worse prognoses.

Stegh and his researchers spent years analyzing this gene more carefully and developing a better understanding of how it functioned, but what they lacked was a mechanism by which to control the gene.

“We didn’t have the technology at hand to really target it and turn this switch back off,” Stegh said. “In GBM the switch is turned on, and we were looking at ways to turn it off.”

Eventually, Stegh teamed up with nanomedicine expert Chad Mirkin, a chemistry professor in the Weinberg College of Arts and Sciences at Northwestern, hoping their combined knowledge could help unravel the mystery of how to control GBM.

“We teamed up with Mirkin, and he developed this amazing nano-technological platform that we call small interfering RNA,” Stegh said. “This is a technology that allows us to regulate gene expression, to turn certain genetic switches back off.”

The small interfering RNA (siRNA), developed by Mirkin, are comprised of balls of RNA structured in a unique, spherical shape, which contains a special core made of gold nanoparticle. As a result of both their unique density and shape, siRNAs are able to cross the body’s blood-brain barrier – which separates the brain from the rest of the body’s circulation – and interact with tumor cells in a way that normal RNA cannot..

“These balls of RNA can engage receptors expressed on tumor cells like a key in a lock,” Stegh said. “They turn on the ability of the cells to internalize these particles and when they are inside they can be used to turn the switches more prevalent in cancer cells off, causing them to die.”

In a study published in the journal Science Translational Medicine, researchers injected siRNA into the blood stream of mice implanted with a human glioma. As a result, the researchers discovered that the mice’s survival rate increased nearly 20 percent, and the sizes of their tumors were reduced three- to four-fold, compared to the control group.

“We were just really excited, because in a cell culture, if you want to deliver RNA or nucleic acid in general…it requires other agents, but in this particle (it didn’t),” Stegh said. “It confirmed to us that these particles really have an amazing capacity to penetrate tissue, and tumor tissue in particular, very effectively.”

Currently, the researchers are testing their treatment on larger animals and hope to soon progress to testing on human subjects as well. Additionally, Stegh said they are hopeful that their therapy can be used to treat other diseases in the future.

“It might not only work in glioblastoma, but in other forms of cancer, particularly those in which our genetic switch might be important for the progression of the disease – for example melanoma or breast cancer,” Stegh said. “Or, to treat other diseases, like those that affect the central nervous system.”