The Ben and Catherine Ivy Foundation Funds MD Anderson Brain Cancer Study with $2 Million

Heimberger Larger Head ShotThe Ben & Catherine Ivy Foundation (Ivy Foundation) announced funding of $2 million for MD Anderson to study ways to shut down a protein in the human body with ties to aggressive brain tumor development and progression.

Transcription factor STAT3 (which stands for signal transducer and activator of transcription 3) has been found to play a key role in the growth brain tumors, such as glioblastoma multiforme (GBM).

A transcription factor is a protein that binds to specific DNA sequences and controls the rate of the transcription of genetic information from DNA to messenger RNA. STAT3 is a type of transcription factor. In humans it is encoded by the STAT3 gene. By shutting down STAT3, researchers hope to halt the growth of an aggressive brain tumor and free up the immune system to fight it.

“We chose to fund MD Anderson’s study to shut down STAT3 because it has the potential to increase patient life expectancy and quality of life, which are two main focus areas of our mission,” said Catherine Ivy, founder and president of the Ivy Foundation.

The transcription factor STAT3 (signal transducer and activator of transcription 3) plays a key role in the development and progression of high-grade malignant gliomas, the most common and aggressive brain tumors. STAT3 is essential for the maintenance of cancer stem cells, and it also protects tumors by suppressing the body’s immune system responses.

Propelled by support from the Ben and Catherine Ivy Foundation, MD Anderson has developed two different ways to shut down STAT3: a small molecule inhibitor designed to halt STAT3 cancer-driving function and a unique nanoparticle that transports a blocking agent to disable the STAT3 signaling pathway in the immune system, thus unleashing that system to destroy the tumor.

“We are very grateful to the Ben and Catherine Ivy Foundation for partnering with us to enable both the preclinical research needed to develop these novel therapeutic strategies and the forthcoming launch of clinical trials that will bring them to patients,” says Amy Heimberger, M.D., the professor of neurosurgery who leads this research. “We believe this work has the potential to change the course of treatment for patients with glioblastoma multiforme and other deadly gliomas by improving survival rates and minimizing toxicity.”

The Ivy Foundation has a research funding focus on glioblastoma multiforme (GBM), the most common and deadliest of malignant primary brain tumors in adults and is the largest privately funded brain cancer research foundation in North America. The Ivy Foundation has invested more than $60 million in brain cancer research since its inception.


NIH Awards $2.8 Million for Study into New Ways to Detect and Treat Brain Injury Resulting From Bleeding in the Brain

TGen, Phoenix Children’s Hospital and Barrow Neurological Institute lead study of traumatic brain injuries following stroke

Developing better treatments and an improved understanding of the biology behind brain injury from hemorrhagic strokes is the main goal of a three-year $2.8 million grant to the Translational Genomics Research Institute (TGen), Phoenix Children’s Hospital, and Barrow Neurological Institute. Announced today, the funding comes from the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) under its Extracellular RNA (ExRNA) Communication program.

Hemorrhagic strokes occur when a blood vessel bursts in the brain and blood accumulates and causes injury to the surrounding brain tissue, often leading to rare but devastating types of traumatic brain injuries (TBIs).

In this study, researchers seek to identify exRNAs suitable as biomarkers to indicate the severity of hemorrhagic stroke and risk of subsequent injury. Biomarkers are indicator molecules — such as proteins, DNA, or RNA — measurable in blood, body fluids or tissue samples that can aid in the diagnosis or severity of a particular disease or the effects of a given treatment.

“Because exRNAs are released from all tissues in the body, including the brain, they make an ideal candidate as a biomarker to help doctors in the evaluation and treatment of patients with brain injury,” said Kendall Van Keuren-Jensen, Ph.D., an Associate Professor in TGen’s Neurogenomics Division, and one of the study’s principal investigators. “Ultimately, this research could lead to the development of new treatments and improved outcomes in hemorrhagic stroke patients.”

In adults, this type of stroke occurs annually in 10-15 people per 100,000, and the risk of these strokes increases with age.

“Scientists still do not fully understand what goes wrong in the brain during and after stroke, and this study will be an important step toward better defining the biological underpinnings of not only stroke, but brain injury in general” said Yashar Kalani, M.D. and Ph.D., a chief resident in Neurological Surgery, assistant professor at Barrow Neurological Institute, and a principal investigator on the study.

The project will focus on two subtypes of hemorrhagic events: aneurysmal subarachnoid hemorrhage; and pediatric intraventricular hemorrhage, which is a significant complication of premature infants.

“We are especially concerned about how these types of brain injury affect children and their ability to recover from such trauma but also develop new and innovative approaches for treating TBI,” said P. David Adelson, M.D., Director of BNI at PCH, Chief Pediatric Neurosurgeon at PCH, and an internationally recognized expert in the area of pediatric traumatic brain injury. He also is one of the study’s principal investigators.

An extracellular RNA (exRNA) biomarker to predict onset and severity of brain hemorrhage would have an immediate effect on improving patient outcomes, as well as to reduce significant costs to patients and caregivers.

Until recently, scientists believed RNA worked mostly inside the cell that produced it. Some types of RNA help translate genes into proteins that are necessary for organisms to function. Other types of RNA control which proteins and how much of those proteins the cells make.

Now, investigators have shown that cells can release RNA — in the form of exRNA — to travel through body fluids and affect other cells. ExRNA can act as a signaling molecule, communicating with other cells and carrying information from cell to cell throughout the body.

A better understanding of basic exRNA biology could open doors to improving the diagnosis, prognosis and treatment of diseases and conditions such as cancer, bone marrow disorders, heart disease, Alzheimer’s disease and multiple sclerosis.

TGen Study Identifies Potential Genes Associated With the Most Common Form of Liver Damage

First-of-its-kind exploratory study shows source of liver damage could be traced by analyzing microRNA

In a first-of-its-kind exploratory study, the Translational Genomics Research Institute (TGen) has identified a potential gene associated with the initiation of the most common cause of liver damage.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver damage. In this study, published in the September edition of Translational Research, TGen scientists sequenced microRNAs (miRNAs) from liver biopsies, spelling out their biochemical molecules to identify several potential gene targets associated with NAFLD-related liver damage.

The miRNAs — RNA molecules that regulate gene expression — were obtained from liver biopsies of 30 female candidates for gastric bypass surgery: 15 with, and 15 without, NAFLD liver damage.

Using the most advanced technology to refine the data, researchers identified several potential gene targets associated with NAFLD-related liver damage. Specifically, they found that a particular miRNA called miR-182 produced a strong association with a protein called FOX03.

“Because of the known role of miR-182 in mechanisms related to liver cancer, we sought to investigate this miRNA in NAFLD-related liver damage by looking at relevant target genes,” said TGen Research Associate Fatjon Leti, the study’s lead author. “We found that levels of FOX03, which has been implicated in liver metabolism, to be significantly decreased.”

Importantly, researchers observed a significant suppression of FOX03 protein levels in damaged livers, compared to those without liver damage, suggesting a potential role for this gene in the initiation of liver disease.

“These finding support a role for liver miRNAs in the disease development of NAFLD-related damage, and yield possible new insight into the molecular mechanisms underlying the initiation and progression of liver damage and eventual liver failure,” said Dr. Johanna DiStefano, Professor and Director of TGen’s Diabetes, Cardiovascular & Metabolic Diseases Division, and the study’s senior author.

“To our knowledge, this is the first study to apply a high-throughput sequencing approach to the investigation of liver miRNAs in NAFLD-related liver damage,” DiStefano said.

The authors cite limitations in this particular study: The study’s small sample, and the fact that all 30 patients were obese females who were candidates for gastric bypass surgery, which may have limited the data. They were selected because obesity is a significant risk factor for NAFLD outcomes, and because of the value of obtaining unbiased liver samples.

“We consider this study an exploratory one, and we acknowledge that validation in a larger, independent dataset will be necessary to confirm our findings,” DiStefano said. “The results reported here do not allow us to make specific conclusions about miRNAs and biological pathways. Additional studies will be necessary to confirm the role of specific miRNAs in liver damage.”

Also contributing to this study — High-throughput sequencing reveals altered expression of hepatic microRNAs in nonalcoholic fatty liver disease-related fibrosis — were the Geisinger Obesity Institute, and Temple University School of Medicine.

This study was supported by TGen, and by the National Institutes of Health (NIH) through grant DK091601.