2013
Highlights
- A Unifying Force: Forging Uncommon Collaborations.
- Channeling Resources: Achieving High-Impact Insights Worldwide.
- Transformative Models: Shaping the Future of Biomedicine.
NEW PATHWAYS FOR DISCOVERY. Solving the greatest scientific challenges in biomedical research requires bold new thinking. We are uniquely positioned to help. We have the know-how to make collaborations thrive…creating environments that are open and neutral, garnering the necessary resources and developing new models.
A Unifying Force: Forging Uncommon Collaborations
A new collaboration focuses on traumatic brain injury
The FNIH has joined with the NIH and the National Football League—a founding partner, thanks to a $30 million donation—to form the Sports and Health Research Program (SHRP), which has taken on brain injury as its first challenge, including the study of the degenerative brain disease known as chronic traumatic encephalopathy, or CTE.
CTE results from repeated trauma to the brain and can lead to dementia, aggression, confusion and depression. Evidence of CTE has been found in the brains of deceased boxers, football players and other athletes. SHRP is bringing together researchers to define criteria for diagnosing CTE in brain tissue and also to determine whether the first signs of CTE can be diagnosed earlier in life through neuroimaging. In 2013, SHRP supported two major cooperative projects involving top CTE and brain injury researchers to understand long-term changes in the brain after head injury or concussions. Six additional pilot projects are working on new ways to diagnose and treat athletes who suffer concussions. SHRP’s work has critical implications for the 1.7 million Americans who suffer traumatic brain injuries each year, including amateur and professional athletes and combat soldiers.
A more efficient model to identify effective breast cancer drugs
Drugs such as tamoxifen and Herceptin® (trastuzumab) target specific characteristics of breast cancer cells. But they do not help all women.
The I-SPY 2 TRIAL, supported by the FNIH Biomarkers Consortium, created a way to evaluate multiple novel anti-cancer compounds in a single clinical trial structure, evaluating the effectiveness of the new treatment by measuring the shrinkage of the tumor prior to surgery. The trial assigns women with high-risk breast cancers to new treatments according to specific genetic or biological traits of that tumor, using adaptive randomization to improve these assignments within the trial and hasten the time to market for successful drugs.
Since 2010, seven compounds from five pharmaceutical companies have been part of I-SPY 2, of which two—neratinib and veliparib—have moved into wider testing (I-SPY 3).
Now a flourishing program, FNIH has turned I-SPY 2 over to QuantumLeap Healthcare Collaborative, a not-for-profit working with the University of California, San Francisco.
Unprecedented data sharing in Alzheimer’s research
As the Alzheimer’s Disease Neuroimaging Initiative (ADNI) approaches the end of its first decade, the partnership remains a gold standard for how academic, industry, advocacy and government partners can, together, advance biomedical research. Involving more than 25 partners coordinated by the FNIH, ADNI created an online, open-access database and image archive for all information collected by researchers.
In ADNI phase 1, this included MRI and PET scans, cerebrospinal fluid and other biosamples from 1,500 participants. Making the information available immediately helps speed everyone’s progress in identifying the biological markers (or biomarkers) that can help trace the progression from normal to mild cognitive impairment to Alzheimer’s Disease—the key to more accurate diagnosis and early intervention. ADNI data have provided the basis for numerous clinical trials and disease-modeling efforts. Several nations are now using similar approaches.
Phase 2, which will continue through 2015, follows phase 1 participants and has enrolled
an additional 750 people. The study has also expanded to include genetic testing, including whole-genome sequencing for more than
800 participants.
Channeling Resources: Achieving High-Impact Insights Worldwide
Insights into improving health for children in developing nations
Young children in resource-poor areas are often caught in a cycle of inadequate nutrition and frequent episodes of diarrhea caused by living in unsanitary conditions. Enteric (intestinal) diseases often undo the benefits of sufficient nutrition, leading to lifelong consequences, such as stunted growth and impaired cognitive development. The $40 million MAL-ED Network, a collaborative project supported by the Bill & Melinda Gates Foundation and managed by the FNIH in collaboration with the NIH Fogarty International Center, supports researchers at eight field sites in Africa, Asia and South America, who have been following more than 1,600 children (more than 200 at each site) since birth to understand how enteric pathogens, nutrition and other environmental factors are linked to physical growth, cognitive development and vaccine response.
Identifying biomarkers that predict growth faltering and/or impaired cognitive development will inform development of strategies for timely intervention. For example, MAL-ED recently found that elevated levels of three substances in the stool of infants may correlate with poorer growth over the subsequent six months, a result consistent in all eight sites, despite environmental differences. These biomarkers may hold promise to help identify children at greatest risk.
New targets for intervening in pulmonary disease
Chronic Obstructive Pulmonary Disease (COPD)—which includes chronic bronchitis and emphysema—affects more than
12 million Americans and is the country’s third leading cause of death. The disease progresses over time, suggesting that there may be points for early intervention to prevent full-blown COPD from developing. However, we do not understand the disease’s clinical course well enough to make that happen.
The SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) program brings together the National Heart, Lung and Blood Institute, the Food and Drug Administration, industry partners and multiple researchers across the country. The study is now enrolling subjects with COPD at 11 sites nationally and collecting blood samples, images, lung function tests and genetic information to determine disease subgroups and to identify biomarkers of disease progression and severity that will be useful as outcome measures in future clinical trials. FNIH coordinates the SPIROMICS External Scientific Board and hosted its meeting in the summer of 2013.
The first medical definition for age-related muscle loss
As people age, they lose skeletal muscle, which eventually can make them weaker, slower, more prone to fall and more dependent—at great cost to the healthcare system and society in general. This condition, called sarcopenia, affects nearly
1 in 3 people over 60 and half of those over age 80. At the moment, there is no standard for the diagnosis of sarcopenia, which limits our ability to understand how it develops and how it might be treated or prevented.
The FNIH Biomarkers Consortium Sarcopenia Project recently generated the first-ever, evidence-based definition for sarcopenia, bringing together the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, academic institutions, the Food and Drug Administration, advocacy groups and five industry partners to analyze data from nine long-term epidemiologic studies involving more than 10,000 healthy people.
FNIH presented the definition in 2012 at a Sarcopenia Consensus Summit and five papers will be published in the spring of 2014. Approaching sarcopenia as a medical condition, rather than a natural outcome of aging, holds great promise for improving the lives of older people.
Transformative Models: Shaping the Future of Biomedicine
Novel approaches to evaluate urgently needed antibiotics
The threat posed by bacterial infections grows, as more strains develop resistance to the current arsenal of antibiotics. Yet, in 2010 regulatory approval for new antibiotics stalled, largely because the endpoints (outcome measures) used to judge effectiveness have been based on antiquated studies.
The FNIH Biomarkers Consortium helped establish consensus on what endpoints should be used in drug trials for Community-Acquired Bacterial Pneumonia (CABP) and Acute Bacterial Skin and Skin Structure Infections (ABSSSI). Partners include the Food and Drug Administration, the NIH’s National Institute of Allergy and Infectious Diseases, the Infectious Diseases Society of America, pharmaceutical companies, biotechnology companies and academic researchers. The team identified two patient-reported outcome measures—symptom improvement within 3 to 5 days for pneumonia and control of lesion spread within 2 to 3 days for skin infection—that have been incorporated into regulatory decision-making criteria and clinical trials.
One new antibiotic has been approved for pneumonia and three for skin infection have cleared phase III testing—the result of well-designed clinical trials that drew on FNIH work. A full set of recommended outcome measures is under development, with completion expected by mid-2014.
A biological approach to stopping dengue fever
Found in 100 countries, with no vaccine and no cure, the mosquito-borne viral disease known as dengue fever is a significant global health threat. Using insecticides to control populations of the female Aedes aegypti mosquito, which spreads the virus, has failed to stop dengue; in fact, incidence has increased 30-fold in the past 50 years.
The FNIH’s Grand Challenges in Global Health, an initiative funded by the Bill & Melinda Gates Foundation, is supporting a global network of researchers who have found that infecting the mosquitoes with Wolbachia, a common bacterium found in many insects, can reduce mosquitoes’ ability to transmit the virus.
The method has shown great promise through a series of test releases in Australia and additional trials are underway in Vietnam, Indonesia and Brazil. Eliminate Dengue is one of several projects that are part of the FNIH’s Vector-based Control of Transmission: Discovery Research (VCTR) program, an offshoot of the Grand Challenges Initiative.
New inspiration for research on gender and Alzheimer’s
In early 2013, the FNIH came together with the Geoffrey Beene Foundation Alzheimer’s Initiative, to initiate a challenge to researchers worldwide, to better understand gender-based differences in the early cognitive decline that leads to Alzheimer’s Disease. Women have a greater risk of developing Alzheimer’s, partly because they live longer than men; however, we know little else about differences in how the disease affects the sexes.
Researchers were invited to “mine the data”—including those available through the Alzheimer’s Disease Neuroimaging Initiative (ADNI)—and present their own hypotheses. In November 2013, after a strict scientific and technical evaluation, Enrico Glaab, Ph.D., a researcher at the Luxembourg Centre for Systems Biomedicine, was selected as the winner. He received $50,000 to continue his study of USP9Y, a protein that is expressed at different levels in men’s and women’s brains and may afford men some protection. The decision was so close, however, that one of the contest’s sponsors, Sanofi, offered $50,000 to fund the second-place winners, Kimberly Glass, Ph.D., and John Quackenbush, Ph.D., of the Dana-Farber Cancer Institute.