2013 ExRNA Projects: Biomarkers

NCATS is administering 18 of the 24 ExRNA Communication projects awarded in 2013. Investigators on 10 of those projects are developing biomarkers from exRNA found in body fluids. Researchers could use these biomarkers to diagnose a variety of diseases and conditions and to predict the course of disease in patients. Specifically, these scientists are exploring biomarkers for Alzheimer’s disease; multiple sclerosis; kidney disease; brain injury; pregnancy complications; heart disease, heart attack and stroke; and liver, stomach and brain cancers.

Circulating MicroRNAs as Disease Biomarkers in Multiple Sclerosis

Investigator: Howard L. Weiner, M.D., Brigham and Women’s Hospital, Boston
Grant Number: UH2-TR000890

Multiple sclerosis (MS) is a disease in which the body’s immune system attacks and destroys the protective covering of the nerves. Over time, the brain, spinal cord and the rest of the body lose the ability to communicate with each other. Many people with MS eventually lose the ability to walk or speak clearly. MS affects 2.5 million people worldwide, including 400,000 in the United States. Currently, no cure exists, but some treatments can slow the disease. A better understanding of the biology and progression of MS could lead to better treatments or a cure. This study team previously measured a type of exRNA called microRNA (miRNA) in the blood of patients with MS and found it was related to disease stage, response to therapy and level of disability. This project’s investigators will continue to study these biomarkers, or indicators of the presence, absence or stage of a disease, and assess their usefulness in diagnosing and monitoring MS progression and response to therapy. MiRNA biomarkers for MS may provide a new way for clinicians to better understand the nature of the disease in individual patients.

Learn more about this project in the NIH RePORTER.

Clinical Utility of Extracellular RNA as Marker of Kidney Disease Progression

Investigators: Thomas Tuschl, Ph.D., The Rockefeller University, New York, and Manikkam Suthanthiran, M.D., Weill Cornell Medical College, New York
Grant Number: UH2-TR000933

Chronic kidney disease (CKD) is a condition in which the kidneys partly or completely lose their ability to function and can result from high blood pressure, diabetes, disorders of the immune system, genetic defects and developmental disorders. CKD causes early death from heart disease, infections and cancer. Many CKD patients develop end-stage kidney disease and need dialysis or kidney transplants. Recipients of kidney transplants also are prone to CKD. Current tests cannot predict which patients will have CKD that worsens over time. Identifying CKD patients at risk for disease progression could allow clinicians to treat patients earlier and slow further decline in kidney function. It also could help scientists develop therapies that prevent decline in kidney function in patients at risk. This research team will identify types of exRNA in the urine of CKD patients and will determine if this approach can identify patients at risk for worsening disease. The teams plans to use these findings to develop a urine test that clinicians can use to guide treatment of CKD patients.

Learn more about this project in the NIH RePORTER.

Clinical Utility of MicroRNAs as Diagnostic Biomarkers of Alzheimer’s Disease

Investigators: Julie Anne Saugstad, Ph.D., and Joseph M. Quinn, M.D., Oregon Health and Science University, Portland
Grant Number: UH2-TR000903

Alzheimer’s disease (AD) is the most common form of dementia and is the sixth leading cause of death in the United States. AD symptoms include memory loss, personality changes and trouble thinking, and the disease typically worsens over time. Current AD treatments cannot stop the disease from progressing, but they can slow the development of symptoms temporarily. Currently, clinicians diagnose AD by noting the degree of a patient’s mental decline, which is not obvious until severe and permanent brain damage has occurred. No biomarkers exist that can be used to predict the onset of AD or distinguish early AD from age-related memory loss. ExRNA could have a potentially important role as a diagnostic biomarker for AD. This project team will examine miRNA found in the fluid surrounding the brain and spinal cord for its usefulness as a biomarker to diagnose AD earlier. Earlier diagnosis could allow patients to start treatments sooner, possibly slowing or preventing brain function decline and damage.

Learn more about this project in the NIH RePORTER.

Clinical Utility of Salivary ExRNA Biomarkers for Gastric Cancer Detection

Investigator: David T.W. Wong, D.M.D., D.M.Sc., University of California, Los Angeles
Grant Number: UH2-TR000923

Gastric (stomach) cancer kills about 800,000 people worldwide each year. This cancer is quite deadly because most people do not notice symptoms until the disease has advanced. Studies suggest that exRNA in saliva can be used as a biomarker to detect oral cancer, Sjögren’s syndrome (a disease in which immune cells attack and destroy the glands that produce tears and saliva), pancreatic cancer, breast cancer, lung cancer, and ovarian cancer. This project team will study exRNA in saliva to determine its usefulness as a biomarker to detect gastric cancer. The study will compare exRNA in saliva from people with and without gastric cancer to assess which types of exRNA are specific to gastric cancer. The use of exRNA in saliva as a biomarker of gastric cancer could enable clinicians to perform simple tests to detect and treat gastric cancer at earlier stages.

Learn more about this project in the NIH RePORTER.

ExRNA Biomarkers for Human Glioma

Investigators: Bob S. Carter, M.D., Ph.D., University of California, San Diego, and Fred Hochberg, M.D., Massachusetts General Hospital, Boston
Grant Number: UH2-TR000931

Gliomas are the most common type of brain tumor, and they are hard to diagnose and treat. Surgeons use biopsies — samples of cells or tissues — to diagnose brain tumors. These biopsies are risky for patients because they require removal of tissue from parts of the brain that are important for language or movement. A way to diagnose brain tumors without surgery would improve patients’ quality of life and reduce risk of brain damage. The investigators will analyze the exRNA that brain tumors release into blood or the fluid surrounding the brain and spinal cord. Using state-of-the-art technologies for examining exRNA, this research team will develop new tests for diagnosing tumors without surgery. If successful, this research could lead to a safer form of diagnosis and earlier, more effective treatment of brain tumors. Findings from this research also could be used to improve scientists’ understanding of how patients respond to brain tumor treatments.

Learn more about this project in the NIH RePORTER.

ExRNA Signatures Predict Outcomes After Brain Injury

Investigators: Matthew J. Huentelman, Ph.D., Translational Genomics Research Institute, Phoenix, P. David Adelson, M.D., Phoenix Children’s Hospital, and Robert Spetzler, M.D., St. Joseph’s Hospital and Medical Center, Phoenix
Grant Number: UH2-TR000891

At least 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, and an estimated 5.3 million people live with TBI-related disability. TBIs cost the nation approximately $76.5 billion each year in medical care, rehabilitation and lost productivity. Hemorrhagic strokes — which occur when a blood vessel bursts in the brain and blood accumulates and compresses the surrounding brain tissue — can cause rare but devastating types of TBIs. Scientists still do not fully understand what goes wrong in the brain during and after these strokes. A biomarker to detect patients at risk for poor outcomes following hemorrhagic stroke could lead to better treatments while improving understanding of the biology of the disease. Certain types of exRNA may be used as biomarkers to predict how patients will respond after hemorrhagic stroke. The investigators will identify exRNA biomarkers that can indicate presence of injury and predict a patient’s outcome after stroke. Ultimately, this research could allow for better treatments and outcomes in hemorrhagic stroke patients.

Learn more about this project in the NIH RePORTER.

ExRNAs for Early Identification of Pregnancies at Risk for Placental Dysfunction

Investigator: Louise C. Laurent, M.D., Ph.D., University of California, San Diego
Grant Number: UH2-TR000906

Placental dysfunction occurs when too little blood, carrying oxygen and nutrients, flows from the mother to the fetus in the womb. The condition can cause poor growth of the fetus and dangerously high blood pressure in the mother during pregnancy. Placental dysfunction is a major cause of maternal and fetal disability and death worldwide. Scientists believe that abnormal cell growth and activity in the placenta during the first trimester of pregnancy causes placental dysfunction. However, clinicians usually do not detect placental dysfunction until the late second and third trimesters. Early detection of pregnancies at risk for this disorder would help clinicians prevent or better treat it. This project’s investigators aim to develop such a method by examining whether exRNA in the blood could be used as a biomarker of risk for placental dysfunction. Accurately determining a woman’s risk would enable clinicians to identify high-risk patients so that high blood pressure or poor growth of the fetus can be detected earlier while sparing low-risk patients unnecessary anxiety.

Learn more about this project in the NIH RePORTER.

Extracellular Non-Coding RNA Biomarkers of Hepatocellular Cancer

Investigator: Tushar Patel, M.B., Ch.B., Mayo Clinic, Jacksonville, Florida
Grant Number: UH2-TR000884

Hepatocellular carcinoma (HCC) — the most common type of liver cancer — is becoming more prevalent, yet survival remains poor. The earlier HCC is diagnosed, the better a patient’s chance for survival. Unfortunately, current tests for HCC are not very good at detecting the cancer early enough for clinicians to treat it effectively. HCC cells release several types of exRNA within exosomes, tiny particles produced by most cells that carry exRNA through body fluids. This project is designed to determine if this exRNA can be used as a biomarker to indicate the presence of HCC in a patient. The investigator also aims to develop a clinically useful way to detect and measure these potential biomarkers and determine their usefulness in identifying patients with HCC earlier than current methods allow.

Learn more about this project in the NIH RePORTER.

Extracellular RNAs: Biomarkers for Cardiovascular Risk and Disease

Investigator: Jane E. Freedman, M.D., University of Massachusetts Medical School, Worcester
Grant Number: UH2-TR000921

Cardiovascular disease (CVD) is the leading cause of death in the United States. Heart disease and stroke, the most common forms of CVD, have common risk factors, including high blood pressure, diabetes, obesity, cigarette smoking and high cholesterol. Certain types of exRNA in the blood affect development and progression of CVD. Researchers have found connections between some of this exRNA and specific forms of CVD. The amounts and types of exRNA may change over time or due to the presence of certain CVD risk factors. Different types of this exRNA could be useful as biomarkers to predict CVD events. To test this possibility, the project team will use blood samples to look for links between exRNA and the presence of CVD. The investigators ultimately will attempt to develop a quick and effective blood test for CVD and its risk factors, using exRNA as a biomarker.

Learn more about this project in the NIH RePORTER.

Plasma MiRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction

Investigators: Saumya Das, M.D., Ph.D., and Anthony Rosenzweig, M.D., Beth Israel Deaconess Medical Center, Boston; Raymond Y. Kwong, M.D., M.P.H., and Marc Sabatine, M.D., M.P.H., Brigham and Women’s Hospital, Boston
Grant Number: UH2-TR000901

Each year, complications from heart attacks (also called myocardial infarctions) contribute to more than half a million cases of heart failure and 300,000 cases of sudden cardiac arrest, which occurs when the heart stops suddenly. Both of these conditions are closely related to changes in the structure and function of the heart — called remodeling — that follow a heart attack. Current tests to predict which patients are at risk for these complications are not accurate enough. This team of investigators will (1) identify miRNA that is related to poor heart remodeling, (2) test the ability of this miRNA to predict poor remodeling in animal models of heart disease, and (3) assess whether miRNA can predict which patients are at risk for poor health outcomes after heart attacks. This miRNA could replace current tests by more accurately identifying patients at higher risk and in need of more frequent monitoring and medical care.

Learn more about this project in the NIH RePORTER.

Descriptions are distilled from grant application abstracts.