An investigational new drug called NU-0129 with a novel spherical nucleic acid structure was recently granted FDA approval to enter an early-stage clinical trial for the treatment of glioblastoma multiforme, an aggressive and deadly form of brain cancer.1,2

Glioblastoma is diagnosed in approximately 30,000 people in the United States each year. Current treatments include chemotherapy, radiation, and surgery. Life expectancy after diagnosis is 14 to 16 months. “We desperately need an effective treatment for this deadly disease,” said Priya Kumthekar, MD, an assistant professor of neurology and hematology-oncology at Feinberg and a Northwestern Medicine neuro-oncologist and lead investigator of the Northwestern trial.

The drug is designed to target the gene BCL2L12, which is overexpressed in glioblastoma tumors. It is comprised of short segments of RNA that are densely arranged on the surface of spherical gold nanoparticles. The spherical structure of the drug allows it to cross the blood-brain barrier, unlike linear RNA, and penetrate the tumor. Once inside the tumor the drug targets the BCL2L2 gene and acts as a dimer switch selectively stopping protein production and causing tumor death.

NU-0129 was first tested in mice in 2013 where it was intravenously injected. The survival rate of mice with glioblastoma increased nearly 20%, and tumor size was reduced 3-fold to 4-fold compared to the control group. “We know this drug works in mice. Now we need to know if it can cross the human blood-brain barrier and accumulate in the tumor of a human being,” said Alexander Stegh, assistant professor of neurology at Northwestern University Feinberg School of Medicine who identified the BCL2L12 gene in 2007.

“If the spherical nucleic acids cross the barrier and localize in the brain, the implications go beyond glioblastoma,” said Chad A. Mirkin, PhD, George B. Rathmann Professor of Chemistry at the Weinberg College of Arts and Sciences, director of the Northwestern International Institute for Nanotechnology (IIN), and creator of the spherical nucleic acid platform. “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.” 

References

1. Jensen SA, Day ES, Ko CH, et. al. Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma. Science Translational Medicine. 2013 Oct. 30. doi: 10.1126/scitranslmed.3006839 [Epub ahead of print]

2. Paul M, Fellman M. First spherical nucleic acid drug injected into humans targets brain cancer [news release]. Chicago, IL: Northwestern University; May 11, 2017. https://news.northwestern.edu/stories/2017/may/spherical-nucleic-acid-drug-human-brain-cancer-glioblastoma/. Accessed June 1, 2017.