Trial to Test Spherical Nanotech Brain Cancer Drug

Spherical nucleic acid (Mirkin Research Group, Northwestern University)

12 May 2017. An early-stage clinical trial will soon begin testing spherically-shaped nanoscale particles to treat glioblastoma, an aggressive form of brain cancer. Northwestern University medical center in Chicago, which developed the drug technology, says the U.S. Food and Drug Administration approved its investigational new drug application, making possible a study of the treatments’ safety.

Glioblastoma is a cancer that forms in the brain’s glial cells that support the functioning of neurons in the brain sending and receiving nerve signals. The cancer generally grows and spreads quickly, often resulting death within 15 months of diagnosis. American Association of Neurological Surgeons estimates glioblastoma, also known as glioblastoma multiforme, occurs in 2 to 3 out of 100,000 adults per year, and accounts for 52 percent of all primary brain tumors.

The drug technology called spherical nucleic acids to treat glioblastoma results from a collaboration between the labs of biochemist and materials scientist Chad Mirkin and neurologist Alexander Stegh. Spherical nucleic acids are densely packed particles, with nucleic acids like those in the genetic materials DNA and RNA, around a spherical core. Their nanoscale size and shape, say the researchers, enable the particles to efficiently enter cells, and once inside regulate genetic processes of those cells. Spherical nucleic acids can also be programmed to assemble like building blocks into more complex structures.

The spherical nucleic acid treatment being tested in the trial, code-named NU-0129, is designed to cross the blood-brain barrier, an obstacle often faced by drugs addressing brain disorders. It contains pieces of RNA packed on the surface of gold nanoparticles, which target the gene BCL2L12 that regulates apoptosis, or programmed cell death. Preclinical studies with lab animals, say the researchers, indicate the treatments work as designed.

“We know this drug works in mice,” says Stegh in a university statement. “Now we need to know if it can cross the human blood-brain barrier and accumulate in the tumor of a human being.” The clinical trial is focused almost entirely on the treatments’ safety, with the research team led by brain cancer specialist Priya Kumthekar, looking primarily for signs of adverse events in the 8 glioblastoma patients. The researchers will also measure concentrations of NU-0129 in blood and ability of the drug to penetrate the patients’ brain tumors. Progression-free and overall survival among the patients will be tracked as well.

The design of the therapy suggests the same approach could be applied to other neurological conditions. “If the spherical nucleic acids cross the barrier and localize in the brain,” notes Mirkin, “the implications go beyond glioblastoma. This would give us the ability to target diseases of the brain by targeting pathways that we know are associated with different diseases, including Huntington’s, Parkinson’s, and Alzheimer’s diseases.”

Northwestern University developed NU-0129 without funding from a pharmaceutical company, which is considered unusual in the industry. “We want to get the drug to patients as quickly as possible,” says Jay Walsh, the university’s vice president for research. “We want to move the drug forward because there are patients with a disease with no current cure.”

In the following video, the researchers tell more about spherical nucleic acids and the clinical trial.

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