Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Incurable Brain Cancer Gene Is Silenced

Published: Wednesday, November 06, 2013
Last Updated: Wednesday, November 06, 2013
Bookmark and Share
Gene regulation technology increases survival rates in mice with glioblastoma.

Glioblastoma multiforme (GBM), the brain cancer that killed Sen. Edward Kennedy and kills approximately 13,000 Americans a year, is aggressive and incurable. Now a Northwestern University research team is the first to demonstrate delivery of a drug that turns off a critical gene in this complex cancer, increasing survival rates significantly in animals with the deadly disease.

The novel therapeutic, which is based on nanotechnology, is small and nimble enough to cross the blood-brain barrier and get to where it is needed -- the brain tumor. Designed to target a specific cancer-causing gene in cells, the drug simply flips the switch of the troublesome oncogene to “off,” silencing the gene. This knocks out the proteins that keep cancer cells immortal.

In a study of mice, the nontoxic drug was delivered by intravenous injection. In animals with GBM, the survival rate increased nearly 20 percent, and tumor size was reduced three to four fold, as compared to the control group. The results are published today (Oct. 30) in Science Translational Medicine.

“This is a beautiful marriage of a new technology with the genes of a terrible disease,” said Chad A. Mirkin, a nanomedicine expert and a senior co-author of the study. “Using highly adaptable spherical nucleic acids, we specifically targeted a gene associated with GBM and turned it off in vivo. This proof-of-concept further establishes a broad platform for treating a wide range of diseases, from lung and colon cancers to rheumatoid arthritis and psoriasis.”

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.

Glioblastoma expert Alexander H. Stegh came to Northwestern University in 2009, attracted by the University’s reputation for interdisciplinary research, and within weeks was paired up with Mirkin to tackle the difficult problem of developing better treatments for glioblastoma.

Help is critical for patients with GBM: The median survival rate is 14 to 16 months, and approximately 16,000 new cases are reported in the U.S. every year.

In their research partnership, Mirkin had the perfect tool to tackle the deadly cancer: spherical nucleic acids (SNAs), new globular forms of DNA and RNA, which he had invented at Northwestern in 1996, and which are nontoxic to humans. The nucleic acid sequence is designed to match the target gene.

And Stegh had the gene: In 2007, he and colleagues identified the gene Bcl2Like12 as one that is overexpressed in glioblastoma tumors and related to glioblastoma’s resistance to conventional therapies.

“My research group is working to uncover the secrets of cancer and, more importantly, how to stop it,” said Stegh, a senior co-author of the study. “Glioblastoma is a very challenging cancer, and most chemo-therapeutic drugs fail in the clinic. The beauty of the gene we silenced in this study is that it plays many different roles in therapy resistance. Taking the gene out of the picture should allow conventional therapies to be more effective.”

Stegh is an assistant professor in the Ken and Ruth Davee Department of Neurology at the Northwestern University Feinberg School of Medicine and an investigator in the Northwestern Brain Tumor Institute.

The power of gene regulation technology is that a disease with a genetic basis can be attacked and treated if scientists have the right tools. Thanks to the Human Genome Project and genomics research over the last two decades, there is an enormous number of genetic targets; having the right therapeutic agents and delivery materials has been the challenge.

“The RNA interfering-based SNAs are a completely novel approach in thinking about cancer therapy,” Stegh said. “One of the problems is that we have large lists of genes that are somehow disregulated in glioblastoma, but we have absolutely no way of targeting all of them using standard pharmacological approaches. That’s where we think nanomaterials can play a fundamental role in allowing us to implement the concept of personalized medicine in cancer therapy.”

Stegh and Mirkin’s drug for GBM is specially designed to target the Bcl2Like12 gene in cancer cells. Key is the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells, but these spherical nucleic acids can. Small interfering RNA (siRNA) surrounds a gold nanoparticle like a shell; the nucleic acids are highly oriented, densely packed and form a tiny sphere. (The gold nanoparticle core is only 13 nanometers in diameter.) The RNA’s sequence is programmed to silence the disease-causing gene.

“The problems posed by glioblastoma and many other diseases are simply too big for one research group to handle,” said Mirkin, who also is the director of Northwestern’s International Institute for Nanotechnology. “This work highlights the power of scientists and engineers from different fields coming together to address a difficult medical issue.”

Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the technology now is the basis of powerful commercialized and FDA-cleared medical diagnostic tools. This new development, however, is the first realization that the nanostructures injected into an animal naturally find their target in the brain and can deliver an effective payload of therapeutics.

The next step for the therapeutic will be to test it in clinical trials.

The nanostructures used in this study were developed in Mirkin’s lab on the Evanston campus and then used in cell and animal studies in Stegh’s lab on the Chicago campus.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Uncovering the Spread of Bacteria in Pneumonia
Northwestern Medicine scientists have discovered the role a toxin produced by a pneumonia-causing bacterium plays in the spread of infection from the lungs to the bloodstream in hospitalized patients.
Tuesday, July 21, 2015
New Drug Reverses Anticoagulant Effects of Blood Thinner
An investigational drug has been shown to reverse the anticoagulant effects of dabigatran in patients who present with bleeding or need for emergent surgery.
Thursday, July 16, 2015
Uncovering Mechanisms of Replication in HPV
The study describes two cellular proteins which are key regulators in the replication of Human Papilloma Virus.
Friday, May 22, 2015
Healing Plants Inspire New Psychiatric Drugs
Treatments used by traditional healers in Nigeria have inspired scientists to synthesize four new chemical compounds that could lead to better therapies for people with psychiatric disorders.
Wednesday, May 13, 2015
DNA Suggests All Early Eskimos Migrated from North Slope
First evidence to genetically tie all Inuit populations to Alaska's North Slope.
Wednesday, May 06, 2015
First Liquid Nanolaser Developed
Technology could lead to new way of doing ‘lab on a chip’ medical diagnostics.
Monday, April 27, 2015
Cancer Genes Turned Off In Deadly Brain Cancer
New therapy approach goes directly to the source of cancer development.
Tuesday, April 07, 2015
Blood Test To Diagnose Depression
Test identifies nine blood markers tied to depression; predicts who will benefit from therapy.
Thursday, September 18, 2014
Big Multiple Sclerosis Breakthrough
Phase 1 trial safely resets patients’ immune systems, reduces attack on myelin protein.
Tuesday, June 11, 2013
Single-Cell Transfection Tool Enables Added Control for Biological Studies
Northwestern University researchers have developed a new method for delivering molecules into single, targeted cells through temporary holes in the cell surface.
Thursday, May 23, 2013
Recent Study Finds That Transplanting People’s Own Stem Cells Can Help Treat Heart Disease
A recent study showed that transplanting a potent form of adult stem cells into the heart muscle of subjects results in less pain and an improved ability to walk.
Friday, November 27, 2009
Brain Starvation as We Age Appears to Trigger Alzheimer’s
A slow, chronic starvation of the brain as we age appears to be one of the major triggers of a biochemical process that causes some forms of Alzheimer's disease.
Tuesday, December 30, 2008
Researcher Transplants Stem Cells to Try to Save Patients' Legs
The first two subjects in the 20-site U.S. trial recently underwent the stem cell transplant process at Northwestern Memorial Hospital.
Thursday, January 24, 2008
Northwestern Exposing Most Deadly Infectious Diseases in 3-D
A scientist slides on a pair of plastic 3-D glasses and an unearthly blue multi-armed creature—an image right out of a sci-fi horror flick—seems to leap out of the computer screen into the laboratory.
Friday, November 02, 2007
First Study Transplanting Angina Patients' Purified Stem Cells Shows Safety and Symptom Relief
The study provided evidence that the procedure is safe and produced a reduction in angina pain as well as improved functioning in patients' daily lives.
Wednesday, June 27, 2007
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
Researchers Find U.S. Breast Milk is Glyphosate Free
Washington State University scientists have found that glyphosate, the main ingredient in the herbicide Roundup, does not accumulate in mother’s breast milk.
Peering into the Vapors
Research suggests that e-cigarettes are much less harmful than previous studies have indicated.
New Technique for Mining Health-conferring Soy Compounds
A new procedure devised by U.S. Department of Agriculture (USDA) scientists to extract lunasin from soybean seeds could expedite further studies of this peptide for its cancer-fighting potential and other health benefits.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Tracking Breast Cancer Before it Grows
A team of scientists led by University of Saskatchewan researcher Saroj Kumar is using cutting-edge Canadian Light Source techniques to screen and treat breast cancer at its earliest changes.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
DNA Damage Seen in Patients Undergoing CT Scanning
Along with the burgeoning use of advanced medical imaging tests over the past decade have come rising public health concerns about possible links between low-dose radiation and cancer.
The Light of Fireflies for Medical Diagnostics
EPFL scientists have exploited the light of fireflies in a new method that detects biological molecules without the need for complex devices and high costs.
Rice Disease-Resistance Discovery Closes the Loop for Scientific Integrity
Researchers reveal how disease resistant rice detects and responds to bacterial infections.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!