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NIH Research Update

10 New NIH Research Highlights

With NIH support, scientists across the United States and the world conduct wide-ranging research to improve the health of our nation. Here's a small sample of recent research accomplishments made by NIH-supported scientists.

Breast Cancer Tumor Test May Help Women Avoid Chemotherapy

A new test may help some women diagnosed with early-stage breast cancer avoid unnecessary chemotherapy treatment. The National Cancer Institute sponsored a large clinical study to determine the types of tumors that would benefit from chemotherapy.

Participants included more than 10,000 women who had recently been diagnosed with hormone-receptor positive, human epidermal growth factor receptor type 2 (HER2) negative breast cancer that had not spread to the lymph nodes. Scientists used a diagnostic gene test called the 21-gene recurrence score (Oncotype DX® Recurrence Score, Genomic Health, Inc.) to help predict the usefulness of chemotherapy and the likelihood of breast cancer recurrence.

The results: 16 percent of women had a test result indicating a very low risk for recurrence. These women did not receive chemotherapy, but did receive standard hormone therapy. Researchers followed up five years later and found that the risk for any breast cancer recurrence for these women was less than 2 percent, and the risk for a recurrence at a distant site was less than 1 percent. The overall survival rate was 98 percent. However, while the study was in 10,000 patients, these results only refer to the 16 percent with the lowest score. Researchers are still waiting for results for the randomized portion of the study. But these findings suggest that gene testing may help guide treatment choices in the future.

NIH-Supported Researchers Earn Prestigious Awards

Groundbreaking NIH-funded research often receives top scientific honors. In 2015, these honors included three NIH-supported Nobel Prize winners:

  • Paul Modrich, PhD, of Howard Hughes Medical Institute and Duke University School of Medicine, and Aziz Sancar, MD, PhD, of the University of North Carolina at Chapel Hill, shared the chemistry prize. It honored the mapping at a molecular level of how cells repair damaged DNA and safeguard genetic information.
  • Angus Deaton, PhD, of Princeton University, was awarded the economics prize. His recent work examined the impact of the financial crisis on well-being in the United States. It also examined how subjective measures of well-being vary across people in different societal groups and in different countries.

Two NIH-funded researchers received top awards from the Lasker Foundation in 2015:

  • Stephen J. Elledge, PhD, of Harvard Medical School and Brigham and Women's Hospital, shared the Albert Lasker Basic Medical Research Award. It honors discoveries concerning the DNA-damage response, a fundamental mechanism that protects the genomes of all living organisms.
  • James P. Allison, PhD, of University of Texas MD Anderson Cancer Center, received the Lasker-DeBakey Clinical Medical Research Award. It recognized the discovery and development of a monoclonal antibody therapy that unleashes the immune system to combat cancer.

A Comparison of Blood Pressure Control Targets

High blood pressure has no noticeable symptoms, but if left untreated can cause serious health problems.

Currently, the standard treatment for patients with hypertension is a systolic target of 140 mmHg. But in 2015, the National Heart, Lung, and Blood Institute, along with other NIH components, sponsored a large clinical study to determine if a more intensive treatment—a target goal of less than 120 mmHg—would be more beneficial for patients with high blood pressure.

More than 9,300 patients ages 50 and older with increased cardiovascular risk were enrolled in the study. Researchers concluded that, compared with the 140 mmHg target, a target systolic pressure of 120 mmHg reduced cardiovascular events, such as stroke, heart attack, and heart failure, by 25 percent. Risk for death was also reduced by 27 percent. Adverse events occurred in both groups, but results suggest that the benefits outweigh these risks.

Researchers ID Genes to Help Predict Heart Disease Risk and Statin Benefits

Healthy lifestyle choices can often help prevent or treat heart disease. If lifestyle changes aren't enough, medicines such as statins can help. But genetics also play a role in heart disease risk, particularly genetic variations known as single-nucleotide polymorphisms (SNPs).

Funded in part by the National Heart, Lung, and Blood Institute, researchers asked if a composite of SNPs could predict heart disease risk and determine who might benefit most from statin therapy. Researchers analyzed data from five studies that included more than 48,000 people who experienced nearly 3,500 heart-disease related events. They then calculated a genetic risk score based on 27 heart disease-associated SNPs, and divided each participant into a low, intermediate, and high genetic risk category. Compared with the other groups, people with the highest genetic risk had an increased risk for coronary heart disease, and a 70 percent greater risk for a heart attack. Genetic risk score also predicted the ability of statin therapy to reduce the risk for heart attack or other heart disease-related events.

These findings suggest that people with the highest genetic risk may benefit the most from statin therapy. This may lead to targeted therapies for patients at risk for heart disease.

Non-surgical Treatment Helps Paralyzed Men Get Moving

In 2015, researchers reported that a surgically stimulating device allowed paralyzed men to regain leg movement. In a follow-up study, scientists tested a nonsurgical strategy for stimulating the spinal cord, known as transcutaneous stimulation. This method sends an electrical current to the spinal cord through electrodes placed on the skin over the spine. The follow-up study included five men who were each paralyzed for more than two years. Each participant received 18 weekly sessions of spinal stimulations for 45 minutes. The men also received muscle conditioning by a therapist, and twice-daily doses of buspirone during the last four weeks of the study.

At first, spinal stimulation only allowed for involuntary step-like movements. But after four weeks, their range of motion was doubled. By the end of the study, the men's legs could move with no stimulation at all, and their range of movement equaled that during spinal stimulation, on average. Electrical signals in the participants' calf muscles also increased over time—suggesting a re-establishment of communication between the brain and spinal cord.

The researchers are assessing if these men can be trained to fully bear their weight. The work was funded in part by the National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences, and other NIH components.

Researchers Identify Energy-Burning Fat Cells

Humans have both white and brown fat cells. Brown fat burns energy and helps maintain body temperature, while white fat stores excess calories. Too much white fat can cause obesity and metabolic disorders.

But researchers recently discovered another type of fat cell: beige. These fat cells appear in white fat cells, but can burn calories like brown fat cells. How beige cells form, however, is uncertain, and brown fat can be difficult to find in humans.

In a study funded in part by NIH's National Institute of Diabetes and Digestive and Kidney Diseases, researchers aimed to better characterize brown and beige fats on a cellular level in adults. After obtaining human fat cells, researchers discovered that genes active in the human cells were similar to those active in mouse beige fat cells, but not in mouse brown fat cells. Analysis of two of the genes in mice revealed that the genes were required for beige fat cells to become brown fat cells, as well as to burn energy to create heat. In the future, these findings may help scientists engineer fat cells to address obesity.

Multiple Sclerosis Patients May Benefit From Immune System Reboot

According to the three-year results of an ongoing clinical trial funded by the National Institute of Allergy and Infectious Diseases, high-dose immunosuppressive therapy with autologous hematopoietic cell transplant (HDIT/HCT) is a promising treatment for early-stage multiple sclerosis (MS).

HDIT/HCT allows doctors to reset a patient's immune system. This is done by collecting hematopoietic stem cells (HSCs), which are cells that eventually develop into blood cells. Then, high-dose chemotherapy and other drugs deplete the patient's immune system. Finally, the patient is infused with his or her own HSCs, which produce red and white blood cells that re-establish the patient's immune system.

The results of the clinical trial so far show that nearly 80 percent of those treated with HDIT/HCT survived without an increase in disability, relapse of MS symptoms, or new brain lesions. Currently, researchers believe this is most applicable to those with early-stage relapsing-remitting MS, the most common form of MS. Research is ongoing to further evaluate the benefits and risks of HDIT/HCT for those with MS.

Eating Peanut-containing Foods in Early Childhood Reduces Peanut Allergy

A recent New England Journal of Medicine study suggests that infants who begin consuming peanut-containing foods early and continued through age 5 are less likely to develop a peanut allergy than those who avoid these foods. Researchers followed more than 600 infants at high risk for peanut allergy for about five years. The infants were randomly assigned to either avoid peanut entirely or to regularly eat at least 6 grams of peanut protein, such as smooth peanut butter, every week.

The results showed that eating peanut-containing foods caused an 80 percent reduction in the development of peanut allergy for those who ate them regularly beginning at an early age. While this research shows promise for preventing peanut allergy, the researchers cautioned parents of children with increased risk—such as those with eczema or egg allergies—to consult an allergist or pediatrician before giving their kids peanut products. The study was funded primarily by NIH's National Institute of Allergy and Infectious Diseases.

End-of-Life Care for Dementia Greatly Outpaces Other Diseases

Those living with dementia face far higher health care costs than for those living with other diseases like cancer or heart disease. That's according to a recent study in Annals of Internal Medicine. Researchers reviewed data on more than 1,700 Medicare beneficiaries age 70 and older who died between 2005 and 2010. While Medicare covers most medical costs for those over age 65, expenses like home care and medical equipment aren't always included.

For those with dementia, the average total health care cost was greater than $287,000 in the last five years of life. That was significantly higher than the average health care cost for those who died of heart disease ($175,000), cancer ($173,000), and other causes ($197,000). The average out-of-pocket costs associated with treating dementia was more than $61,522, which was 81 percent higher than those without the disease ($34,068).

The study, which is supported by the National Institute on Aging, provides a critical look at the cost of treating dementia and the financial burden many families face.

Cataloging Human Genetic Variation Around the World

A team of international scientists has collected the world's largest assortment of human genetic differences in various populations around the globe. These data provide researchers with a powerful tool to study how genetic variation affects disease risk and drug response for treatment.

The 1000 Genomes Project Consortium, partially funded and directed by the National Human Genome Research Institute, a part of NIH, published the results in two studies in the journal Nature. The researchers sequenced the genomes of more than 2,500 people from 26 populations across Africa, East and South Asia, Europe, and the Americas. In the main paper, researchers identified about 88 million sites in the human genome that vary among people. The majority of these—about 84.7 million—were differences in a single DNA building block called single nucleotide polymorphisms (SNPs).

In the companion article, researchers found 69,000 rarer structural variants in the genome. While less common than SNPs, these variants were much more likely to be associated with traits such as disease risk. Researchers hope these data increase the understanding of variations in genomes and provide a foundation for better insights into human disease genomics.

3-D Printing Holds Promise for Nerve Regeneration

Treatment for peripheral nerve damage varies depending on the type of injury, and current treatment options typically rely on grafting a portion of healthy nerve to help replace the damaged section. This type of treatment is limiting, however, and can have negative health outcomes for patients.

As a result, researchers have been investigating other techniques to guide nerve regeneration, one of which includes using a 3-D printer to mimic naturally branching nerves. To create a customized, 3-D printed nerve scaffold, a section of the nerve is removed and a cast is prepared. A 3-D light scan is conducted at various angles, and a 3-D model of the nerve pathway can then be printed.

So far, this method has been used on damaged sciatic nerves in rats, improving the animals' ability to walk within three months. As this technique develops, scientists hope this technique may be used to create a range of customized nerve scaffolds to aid in cell regeneration. Research was funded by in part by NIH's National Institute of Neurological Disorders and Stroke and National Heart, Lung, and Blood Institute.

Spring 2016 Issue: Volume 11 Number 1 Page 24-28