These findings may help settle the debate regarding resveratrol’s biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation, and cancer. The study appears in the February 3rd issue of the journal Cell [1].

Lead study author Jay H. Chung, M.D., Ph.D., chief of the Laboratory of Obesity and Aging Research at the NIH’s National Heart, Lung, and Blood Institute, said:

Resveratrol has potential as a therapy for diverse diseases such as type 2 diabetes, Alzheimer’s disease, and heart disease. However, before researchers can transform resveratrol into a safe and effective medicine, they need to know exactly what it targets in cells.

Several previous studies suggested that resveratrol’s primary target is sirtuin 1 (SIRT1). Chung and colleagues suspected otherwise when they found that resveratrol activity required another protein called AMP-activated protein kinase (AMPK). This would not be the case if resveratrol directly interacted with sirtuin 1.

In this study, the researchers methodically traced out the metabolic activity in cells treated with resveratrol and identified phosphodiesterase 4 (PDE4) in the skeletal muscle as the principal target for the health benefits of resveratrol. By inhibiting PDE4, resveratrol triggers a series of events in a cell, one of which indirectly activates sirtuin 1 (SIRT1).

To confirm that resveratrol attaches to and inhibits PDE proteins, Chung’s group gave mice rolipram, a drug known to inhibit PDE4. Rolipram reproduced all of the biochemical effects and health benefits of resveratrol, such as preventing diet-induced obesity, improving glucose tolerance, and increasing physical endurance.

Chung noted that because resveratrol in its natural form interacts with many proteins, not just PDEs, it may cause not-yet-known toxicities as a medicine, particularly with long-term use. He added that the levels of resveratrol found in wine or foods are likely not high enough to produce significant health benefits or problems. Convincing clinical studies in humans have used about 1 gram (equal in weight to just under 2 teaspoons of sugar) of resveratrol per day, roughly equal to the amount found in 667 bottles of red wine.

The study results also suggest that inhibitors of PDE4 may offer the benefits of resveratrol without the potential toxicities arising from resveratrol’s interactions with other proteins. One PDE4 inhibitor called roflumilast has already been approved by the FDA for the treatment of chronic obstructive pulmonary disease (COPD).

Robert Balaban, Ph.D., director of the NHLBI Division of Intramural Research, said:

This result underscores the need for careful, well-controlled studies to illuminate how these natural products operate. As Dr. Chung’s work suggests, the effects of resveratrol seem to be more complicated than originally thought. However, this new insight into the phosphodiesterases might prove an interesting avenue to pursue.

Source: NIH News

References

1. Park et al. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases. Cell. 2012 Feb 3;148(3):421-433.
   View abstract

NCATS will serve as the nation’s hub for catalyzing innovations in translational science. Working closely with partners in the regulatory, academic, nonprofit, and private sectors, NCATS will strive to identify and overcome hurdles that slow the development of effective treatments and cures.

NIH Director Dr. Francis S. Collins, M.D., Ph.D., said:

Congressional support for the National Center for Advancing Translational Sciences marks a major milestone in mobilizing the community effort required to revolutionize the science of translation. Patients suffering from debilitating and life threatening diseases do not have the luxury to wait the 13 years it currently takes to translate new scientific discoveries into treatments that could save or improve the quality of their lives. The entire community must work together to forge a new paradigm, and NCATS aims to catalyze this effort.

A prime example of the type of innovative projects that will be led by NCATS is the new initiative between NIH, the Defense Advanced Research Projects Agency, and the U.S. Food and Drug Administration to develop cutting-edge chip technology. This new technology will allow researchers to screen for safe and effective drugs far more swiftly and efficiently than current methods. A great deal of time and money can be saved testing drug safety and effectiveness much earlier in the process.

To meet the goals of NCATS, NIH is reorganizing a wide range of preclinical and clinical translational science capabilities within NIH into an integrated scientific enterprise with new leadership and a bold new agenda. While the effort to recruit an NCATS director continues, organizational changes and realignment of resources will move forward under the leadership of Acting Director Thomas R. Insel, M.D., and Acting Deputy Director Kathy Hudson, Ph.D. Dr. Insel is the director of the National Institutes of Mental Health and Dr. Hudson is the deputy director for science, outreach, and policy at the National Institutes of Health.

The following programs will comprise NCATS:

• Bridging Interventional Development Gaps, which makes available critical resources needed for the development of new therapeutic agents
• Clinical and Translational Science Awards, which fund a national consortium of medical research institutions working together to improve the way clinical and translational research is conducted nationwide
• Cures Acceleration Network, which enables NCATS to fund research in new and innovative ways
• FDA-NIH Regulatory Science, which is an interagency partnership that aims to accelerate the development and use of better tools, standards and approaches for developing and evaluating diagnostic and therapeutic products
• Office of Rare Diseases Research, which coordinates and supports rare diseases research
• Components of the Molecular Libraries, which is an initiative that provides researchers with access to the large-scale screening capacity necessary to identify compounds that can be used as chemical probes to validate new therapeutic targets
• Therapeutics for Rare and Neglected Diseases, which is a program to encourage and speed the development of new drugs for rare and neglected diseases

The budget for NCATS is primarily a reallocation of funds from programs previously located in the NIH Office of the Director, National Human Genome Research Institute, and National Center for Research Resources. NIH is committed to both basic and applied research and has maintained a relatively stable ratio of funding across these two areas of focus. The funding ratio will not be disturbed by the establishment of this new center.

The formation of NCATS has been a methodical process highlighted by the recommendation of the NIH Scientific Management Review Board in December 2010 to create a new center dedicated to advancing translational science. This recommendation was followed by a year of intensive feedback and expert insight from all sectors of translational science through advisory meetings and extensive public consultation.

Dr. Collins said:

I am deeply grateful for the expertise and insight provided by the many researchers, industry executives, patients, voluntary organizations, and NIH staff that helped NIH evaluate NCATS’ purpose and crystallize its vision.

To learn more about the impetus and development of NCATS, go to:

• NCATS web page: http://www.nih.gov/about/director/ncats/index.htm
• NCATS on the Feedback NIH website: http://feedback.nih.gov/index.php/category/ncats/

Source: NIH News

The research team comprised of scientists from the National Institute of Environmental Health Sciences (NIEHS), which is part of the National Institutes of Health, and several other institutions, published its data online in the Dec. 19 issue of The Journal of Clinical Investigation [1].

Preclinical research suggests that patients with a variety of vascular conditions, such as diabetes, hypertension, inflammation, stroke, and heart attack may benefit by increasing their EET levels, because the compounds cause blood vessels to dilate and reduce tissue inflammation and cell death. However, previous work has also demonstrated that EETs make tumor cells grow faster and cause them to migrate and become metastatic. Darryl Zeldin, M.D., NIEHS scientific director and author on the paper, said he believed that human metabolism has to achieve a certain harmony in regard to EETs. Zeldin said:

The body has to produce enough EETs to maintain a healthy cardiovascular system without promoting cancer. It has to balance the double-edged sword just right.

To find out how EETs encourage the development of cancer, the team created two mice strains, one with high levels of EETs and one with low levels of EETs. Zeldin explained:

The mice with higher EETs developed more metastatic tumors compared to the mice with lower EETs. Often, the tumor itself will produce more EETs, which can speed up tumor growth and its subsequent spread, but our analysis demonstrated that the EETs produced by the surrounding tissues encouraged tumor growth and migration.

Matthew Edin, Ph.D., a research fellow in Zeldin’s group, is one of the authors on the paper and helped develop the mice strains. He said EETs directly lead to the creation of new blood vessels, also known as angiogenesis, which the cancer cells need in order to receive oxygen and nutrients to grow. He equated the process to what happens when a builder begins constructing a new housing development. According to Edin:

One of the first things construction crews have to do is build the roads, so that materials and workers can be transported to the site. In cancer, EETs accelerate the road building, allowing the housing development to expand quickly.

According to Dipak Panigrahy, M.D., an author on the paper and a research associate at the Dana-Farber/Children’s Hospital Cancer Center, Boston, EETs have a potent stimulatory effect promoting cancer growth and metastasis, a process that could be effectively inhibited using novel antagonists, such as EEZE, which are compounds that interfere with this pathway in mice. EEZE has not been approved for human use, and is only used for research. Panigrahy explained:

EEZE is structurally similar to EETs, but it blocks the effect of EETs and dramatically slows tumorigenesis.

Mark Kieran, M.D., Ph.D., another author of this collaborative study and also from Dana-Farber, commented on the importance of the research:

The identification of an old pathway studied for many years in cardiovascular disease has found a new role in regulating cancer growth and metastasis, the primary causes of cancer related deaths. With these findings, opportunities to better understand the underlying mechanisms that drive cancer, and thus the development of effective therapies for their treatment, moves one step closer to a reality.

Source: NIH News

References

1. Panigrahy et al. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest. 2011.
   View abstract

The children in the study who appeared to have difficulty grasping the fundamental concept of exact numerical quantities — that the printed numeral 3, for example, represents three dots on a page — went on to be diagnosed with math learning disability by fifth grade.

Other early factors correlated with a math learning disability were difficulty recalling answers to single-digit addition problems, distractibility in class, and difficulty understanding that more complex math problems can be broken down into smaller problems that can be solved individually.

Although the math learning disabled children did make limited progress in subsequent grades, by fifth grade they had not caught up to their typically achieving peers in the ability to recall number facts or in their ease of adding sets of dots and numerals together. The authors note that the math disabled students did catch up in other areas, such as the use of counting to solve problems.

The study was not designed to prove cause and effect, so the researchers do not know whether the factors they identified caused the children’s math learning disability or were linked to other, unidentified factors.

Kathy Mann Koepke, Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the study, said:

The search for factors underlying difficulty learning mathematics is extremely important. Once we identify such factors, the hope is that we can modify them through appropriate teaching methods to help people who have difficulty learning and using math.

Dr. Mann Koepke directs the NICHD’s Mathematics and Science Cognition and Learning Development and Disorders program. She said:

Math skills are important for higher education and for entry into many higher paying technical fields. Math skills have many health implications. For example, many American adults lack even the basic math skills necessary to estimate the appropriate number of calories in their diets or to calculate the time intervals at which to take their medications.

The study was conducted by Mary K. Hoard, Ph.D., Lara Nugent, Drew H. Bailey and David C. Geary, Ph.D., all of the University of Missouri, Columbia. Their findings appear in the Journal of Educational Psychology [1].

The researchers’ analysis was based on a battery of tests they gave one to three times each year to 177 students at 12 Columbia, Missouri, public schools. The testing process took place from kindergarten through fifth grade. The researchers measured several factors:

1. math achievement
2. reading ability
3. intelligence and general cognitive ability
4. paying attention in class
5. working memory, the ability to hold one idea or concept in mind while switching between tasks
6. an understanding of numbers and their relation to each other
7. understanding of the number line
8. aptitude for solving simple and complex addition problems

The researchers classified the students into three groups based on their early achievement and the subsequent progress they made in math from kindergarten to fifth grade. One group — referred to as typically achieving students — had average scores in kindergarten and developed their skills at an average rate during their early school years (132 students). Low-achieving students had an average score in kindergarten and made inconsistent and slow progress (29 students). Students with a low initial score and consistently slow progress were described as learning disabled with regard to math (16 students).

After their analysis, the researchers found that differences between groups in kindergarten scores were correlated with the result of one test in particular. For this test, students were asked to look at a series of rectangles, resembling dominoes, on a computer screen. Each domino was each divided into two or three areas; some areas contained one to nine dots, and others a written numeral. Students were asked to quickly circle any dominos in which the number of dots, together with the numeral, matched the target number and to not circle those that did not match.

The researchers found that the difference in scores from this test was linked to the overall gap in math scores between typically achieving and math learning disabled groups.

Dr. Geary said:

Our findings suggest that children who generally struggle with math — the low achievers — may have a poor sense of numbers, but they can narrow the achievement gap in part because most of them can memorize new math facts and, thus, learn some aspects of math as quickly as their typically achieving peers.

He added that, in contrast to the low achievers, students with a math learning disability not only have a poor concept of numbers, but also have difficulty memorizing math facts.

Clarifying the factors that contribute to a math learning disability may lead to the development of teaching methods that help students overcome difficulties with number concepts and skills, Dr. Mann-Koepke said. It is important to identify potential difficulties early, when chances for successfully overcoming them are greatest.

Other NICHD-funded investigators have also identified basic risk factors for math learning disability. These researchers have shown that math skills are linked to the approximate number system, a person’s intuitive ability to estimate quantities or identify the approximate number in a set. One study of grade school children showed that this ability is impaired in children with a math learning disability. A related study showed that difficulty with estimating such quantities is apparent in children as young as 3 and is correlated with later poor math performance in school. Researchers do not yet know if the ability to distinguish between small, exact quantities is related to the approximate number system.

Source: NIH News

References

1. Geary et al. Mathematical cognition deficits in children with learning disabilities and persistent low achievement: A five year prospective study. Journal of Educational Psychology. In press.

In many school systems, the discrepancy model is the criterion for determining whether a child will be provided with specialized reading instruction. With the discrepancy model, children with dyslexia and lower-than-average IQ scores may not be classified as learning disabled and so may not be eligible for special educational services to help them learn to read.

Brett Miller, Ph.D., director of the Reading, Writing and Related Learning Disabilities Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the part of the National Institutes of Health that funded the study, said:

The study results indicate that the discrepancy model is not a valid basis for allocating special educational services in reading. It follows that, whether they have high IQ scores or low IQ scores, children with great difficulty in learning to read stand to benefit from educational services to help them learn to read.

The study findings were published online in Psychological Science [1]. The study was conducted by Fumiko Hoeft, M.D., Ph.D., of Stanford University, in Stanford, Calif., and colleagues at Boston College; York University, in Toronto; and the Massachusetts Institute of Technology, in Cambridge.

Originally, the U.S. Individuals with Disabilities Education Act required the use of the discrepancy model to identify those students who needed assistance for a learning disability. In the 1990s, studies showed that children who had difficulty learning to read had difficulty with phonological awareness — matching printed letters of the alphabet to the speech sounds that those letters represented. Based on these findings, the reauthorization of the Act dropped the requirement that school systems use the discrepancy model. Many school systems, however, retained the discrepancy model as a means to classify students needing special educational services in reading.

The current study showed that, when they engaged in tasks involving phonological awareness, children with dyslexia showed the same patterns of brain activation, regardless of whether or not they had high or low IQ scores in relation to their reading abilities.

To conduct the study, the researchers measured the brain activity of 131 typical and poor readers from schools in the greater Pittsburgh and San Francisco Bay areas, using functional magnetic resonance imaging scanners. The students were from 7 to 16 years old. Based on IQ testing, the students were classified into three groups:

• Typical readers, having typical reading and IQ scores.
• Discrepant poor readers (having poor reading scores and typical IQ scores).
• Poor readers with low IQ scores.

The researchers imaged the children’s brain activity as the students looked at pairs of words on a computer screen and indicated whether they rhymed (bate and gait) or did not rhyme (price and miss). After comparing scans from the three groups, the researchers found no basis for distinguishing between groups of poor readers based on their IQ scores.

Dr. Hoeft said:

These findings suggest there is little reason to rely on the discrepancy model in the classroom any longer. Regardless of IQ, all children with dyslexia should be eligible for support in learning to read.

To learn more about dyslexia, visit the International Dyslexia Association (IDA), a non-profit organization dedicated to helping individuals with dyslexia, their families and the communities that support them.

Source: NIH News

References

1. Tanaka et al. The Brain Basis of the Phonological Deficit in Dyslexia Is Independent of IQ. Psychol Sci. 2011 Nov 1;22(11):1442-51. Epub 2011 Oct 17.
   View abstract

Sickle cell disease is a recessive genetic disorder caused by a single base mutation in the gene for hemoglobin, beta locus (HBB). Hemoglobin is responsible for transporting oxygen throughout the body. People living with sickle cell disease have two copies of an altered gene that produces sickle hemoglobin instead of normal adult hemoglobin. Sickle hemoglobin changes shape after releasing its oxygen, causing the red blood cell to become stiff, misshapen and sticky, and slowing blood flow to tissues. This process damages organs and causes pain.

Susan B. Shurin, M.D., acting director of the NIH’s National Heart, Lung, and Blood Institute, which co-funded the study, said:

This discovery provides an important new target for future therapies in people with sickle cell disease. More work is needed before it will be possible to test such therapies in people, but this study demonstrates that the approach works in principle.

Researchers at Harvard Medical School in Boston and the University of Texas at Austin corrected sickle cell disease in mice that had been bred to have the inherited blood disorder. The National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) — all part of the NIH — funded the research. The results of the study were recently published in the online edition of the journal Science [1].

The study tested a new approach to increasing the production of a third form of hemoglobin — fetal hemoglobin. Production of fetal hemoglobin predominates before birth, but turns off thereafter as adult hemoglobin production takes over. People with sickle cell disease are unable to make normal adult hemoglobin, and instead make sickle hemoglobin starting in infancy.

An elevated level of fetal hemoglobin within the red blood cell reduces the tendency of sickle hemoglobin to change the shape of red blood cells. Considerable NIH- supported research has shown that the drug hydroxyurea increases production of fetal hemoglobin and reduces the number of pain crises and other complications of sickle cell disease in adults and children. However, not all patients respond well to hydroxyurea, and adverse side effects are a concern.

The current study explores a more targeted approach to increasing fetal hemoglobin production. It builds upon earlier studies by Stuart Orkin, M.D., and his team at Harvard Medical School, Children’s Hospital of Boston, and the Howard Hughes Medical Institute, Boston, which discovered that a protein called B-cel CLL/Lymphoma 11A (BCL11A) normally suppresses the production of fetal hemoglobin soon after birth [2]. The researchers viewed the BCL11A protein as a target for therapy and decided to see what would happen if they blocked production of the protein.

Griffin P. Rodgers, M.D., M.A.C.P., director of NIDDK, said:

This important advance in the battle against sickle cell disease is another outstanding example of how great things can happen when work proceeds from bench to bedside, and back to the bench. We hope that one day, this discovery and any that build upon it will translate into a viable treatment option for those suffering from this devastating illness.

The current paper details how the research team silenced the mouse gene that produces the BCL11A protein in mice with sickle cell disease. Silencing the gene turned off production of the BCL11A protein and allowed the adult mice to continue to produce fetal hemoglobin. It appears to have eliminated disease symptoms without affecting other aspects of blood production.

Approximately 100,000 Americans live with sickle cell disease. It is most prevalent in people of African, Hispanic, Mediterranean, and Middle Eastern descent. There is no widely available cure for sickle cell disease. Bone marrow transplants have cured some patients, but the treatment is not without risk and most patients do not have relatives who can donate compatible and healthy bone marrow to them.

Source: NIH News

References

1. Xu et al. Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing. Science. 2011 Oct 13. [Epub ahead of print]
   View abstract
2. Sankaran et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008 Dec 19;322(5909):1839-42.
   View abstract

Go4Life was presented Oct. 19, 2011, at a briefing on exercise and aging on Capitol Hill, hosted by Herb Kohl, D-Wis., Chair of the Senate Special Committee on Aging and by Mark Udall, D-Colo., Senate Special Committee on Aging.

The briefing highlighted the public-private partnership central to the campaign — a Go4Life team that will work to bring the campaign into communities across the United States. The team includes NIH, other agencies in the U.S. Department of Health and Human Services, and national organizations, corporations, insurers, health care providers, and nonprofit organizations.

Go4Life’s participating organizations will incorporate campaign resources into their own health and wellness activities, disseminating Go4Life web links and materials to their members, employees, and customers. Many partners will directly sponsor events or community activities aimed at engaging older adults in exercise and physical activity as the campaign moves forward.

The campaign was conceived, and is being led, by the National Institute on Aging (NIA), the component of NIH devoted to research on aging. The NIA will work with the Go4Life community on events and will highlight participating organizations and their activities on the campaign website.

U.S. Surgeon General, Regina Benjamin, M.D., M.B.A., said:

If we want to become a healthy and fit nation, we need to increase the number of Americans who are healthy at every stage of life. Go4Life provides older adults with the tools and resources to get moving and keep moving. With the release of the National Prevention Strategy, we are moving our health care system from a focus on sickness and disease to a focus on wellness and prevention.

The campaign developed from concerns that, despite proven health benefits, exercise and physical activity rates among older people are low. About 30 percent of people aged 45–64 say they engage in regular leisure-time physical activity. Only a quarter of those ages 65–74 say they do. And while experts say people age 85 and older, can benefit from exercise, only 11 percent of that age group report being active. At the same time, NIA noted, some older adults were contacting the Institute for guidance on kinds of exercises to do, indicating interest in becoming more active.

According to Richard J. Hodes, M.D., director of the NIA:

You’re never too old to increase your level of physical activity and exercise. Go4Life is based on studies demonstrating the benefits of exercise and physical activity for older people, including those with chronic health conditions. This new campaign reaches out to older people who traditionally have not embraced exercise and shows them ways that even those with physical limitations may be able to exercise safely as well.

The research-based resources of Go4Life center on a colorful, interactive website providing information and motivation for exercise for individuals, families and friends, organizations, and health care professionals. The site features specific exercises, success stories, and free materials to motivate growing numbers of older people to start exercising and keep going. It even offers online virtual coaches to help motivate Go4Life participants. Many Go4Life materials are also available in Spanish.

To develop Go4Life, NIA brought together some of the nation’s leading experts on aging, exercise, and motivation. Over two years, the task force reviewed the research and worked with the institute to develop a book, Exercise & Physical Activity: Your Everyday Guide from the National Institute on Aging. The campaign is based on the book.

Some specific benefits of exercise for health and aging include:

• Fitness and cardiorespiratory health: In one study, moderately fit women and men had a 50 percent lower risk of type 2 diabetes, hypertension, coronary heart disease, obesity, and some cancers when compared with their low fit peers. High fit people obtained additional benefit, typically another 10-15 percent lower risk.
• Reduced pain, better function with osteoarthritis: In a clinical trial of people age 60 and older with knee osteoarthritis, those who participated in an aerobic exercise or resistance exercise program reported less pain and better function than those in the group assigned to a health education program.
• Preventing diabetes: Results from the NIH-sponsored Diabetes Prevention Program, which examines ways to prevent or delay the development of non-insulin-dependent diabetes, found that people over age 60 at high risk for diabetes reduced their risk by 71 percent by adopting a moderate exercise routine and a low-fat diet.

Assistant Secretary for Aging Kathy Greenlee, who heads the Administration on Aging at HHS, said:

An important part of active aging is being healthy and staying fit. I look forward to working with NIH and the growing number of campaign partners in the aging network to distribute to seniors around the country these tips on how to get active and stay active.

The NIA invites public and private organizations whose interests and activities involve health, aging and exercise to join the campaign. Agencies, organizations and companies on board as of today as initial Go4Life team members are:

Federal agencies:

• Administration on Aging
• Agency for Healthcare Research and Quality
• Centers for Disease Control and Prevention
• National Institutes of Health
• National Center for Complementary and Alternative Medicine
• National Heart, Lung and Blood Institute
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
• National Institute of Diabetes and Digestive and Kidney Diseases
• National Institute of Mental Health
• National Institute of Neurological Disorders and Stroke
• Office of Disease Prevention and Health Promotion, HHS
• President’s Council on Fitness, Sports & Nutrition

Private and nonprofit organizations:

• Alliance for Aging Research
• America On the Move Foundation, Inc.
• American College of Sports Medicine
• American Federation for Aging Research
• American Geriatrics Society
• American Library Association
• American Medical Association
• American Occupational Therapy Association
• American Physical Therapy Association
• American Psychological Association
• America’s Health Insurance Plans
• CenturyLink
• Easter Seals
• Erickson Living/Greenspring
• Gerontological Society of America
• Humana Inc.
• International Council on Active Aging
• Jewish Community Centers Association of North America
• National Association of Area Agencies on Aging
• National Association of States United for Aging and Disabilities
• National Council on Aging
• National Recreation and Park Association
• National Senior Health & Fitness Day (Mature Market Resource Center)
• OASIS
• Sunrise Senior Living
• U.S. Chamber of Commerce
• Volunteers of America
• Year of Vitality Cleveland
• YMCA of the USA

For further information on the public and private support of the Go4Life initiative, please visit www.nia.nih.gov/Go4Life.

The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The Institute’s broad scientific program seeks to understand the nature of aging and to extend the healthy, active years of life. For more information on research, aging, and health, go to www.nia.nih.gov.

Source: NIH News

These awards are granted under three innovative research programs supported by the NIH Common Fund: the NIH Director’s Pioneer, New Innovator, and Transformative Research Projects Awards. The Common Fund, enacted into law by Congress through the 2006 NIH Reform Act, supports trans-NIH programs with a particular emphasis on innovation and risk taking.

James M. Anderson, M.D., Ph.D., director of the Division of Program Coordination, Planning and Strategic Initiatives, who guides the Common Fund’s High-Risk Research program, said:

The NIH Director’s Award programs reinvigorate the biomedical work force by providing unique opportunities to conduct research that is neither incremental nor conventional. The awards are intended to catalyze giant leaps forward for any area of biomedical research, allowing investigators to go in entirely new directions.

Since inception, the NIH Director’s Award Program has funded a total of 406 High-Risk Research awards: 111 Pioneer Awards since 2004, 216 New Innovator Awards since 2007, and 79 Transformative Research Projects Awards since 2009. This tally includes this year’s 13 Pioneer Awards, 49 New Innovator Awards, and 17 Transformative Research Projects Awards.

The NIH expects to make competing awards of approximately $10.4 million to Pioneer awardees, $117.5 million to New Innovators, and $15.9 million to Transformative Research Projects awardees in Fiscal Year 2011. The total funding provided to this competing cohort over a five-year period is estimated to be $245.6 million.

More information on each of the award programs, including this year’s awardees, can be found below:

• Pioneer Award — http://commonfund.nih.gov/pioneer
• New Innovator Award — http://commonfund.nih.gov/newinnovator
• Transformative Research Projects Award — http://commonfund.nih.gov/T-R01

The NIH Common Fund encourages collaboration and supports a series of exceptionally high impact, trans-NIH programs. The NIH Director’s Awards Program is funded through the Common Fund and managed by the NIH Office of the Director in partnership with the various NIH Institutes, Centers and Offices. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.

Source: NIH News

New enrollment in the study was stopped in April because early data showed significantly more strokes and deaths occurred among the stented patients at the 30-day mark compared to the group who received the medical management alone.

In addition to the intensive medical program, half of the patients in the study received an intervention of a self-expanding stent that widens a major artery in the brain and facilitates blood flow. One possible explanation for the higher stroke rate in the stented group is that patients who have had recent stroke symptoms sometimes have unstable plaque in their arteries which the stent could have dislodged, the study authors suggest. The study device, the Gateway-Wingspan intracranial angioplasty and stenting system, is the only system currently approved by the U.S. Food and Drug Administration (FDA) for certain high-risk stroke patients. The authors noted that although similar stenting systems that do not have FDA approval are being used in clinical practice, they did not evaluate those devices in this study.

The authors also emphasize that the study participants were in the highest risk category, with blockage or narrowing of arteries of 70 to 99 percent. Stroke patients with moderate cerebral arterial blockage (50-69 percent) were excluded because their risk of stroke is low with usual medical management, and researchers thought this group would be unlikely to benefit from stenting.

Walter Koroshetz, M.D., deputy director of NINDS, said:

This study provides an answer to a longstanding question by physicians — what to do to prevent a devastating second stroke in a high risk population. Although technological advances have brought intracranial stenting into practice, we have now learned that, when tested in a large group, this particular device did not lead to a better health outcome.

Stroke is the fourth leading cause of death in the United States. Stenosis, a blockage or narrowing of brain arteries caused by the build-up of plaque, accounts for more than 50,000 of the 795,000 strokes that occur annually nationwide. Stenosis is particularly common in African-Americans, Hispanics, Asian Americans and people with diabetes.

The NIH Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study enrolled 451 patients at 50 sites across the United States. The investigators looked at whether patients had a second stroke or died within 30 days of enrollment, or had a stroke in the same area of the brain from 30 days to the end of follow-up. They had hypothesized that compared to intensive medical therapy alone, the addition of an intracranial stenting system would decrease the risk of a stroke or death by 35 percent over two years.

Instead they found that 14.7 percent of patients (33) in the stenting group experienced a stroke or died within the first 30 days after enrollment, compared with 5.8 percent (13) of patients treated with medical therapy alone. There were five stroke-related deaths within 30 days, all in the stenting group, and one non-stroke-related death in the medical management group. During a follow-up period of just less than one year, 20.5 percent of patients in the stenting group and 11.5 percent of patients in the medical group had a stroke or death, or a stroke in the same area of the brain beyond 30 days, a highly significant difference in favor of the patients in the study’s medical group. Based on these data, the Data and Safety Monitoring Board recommended that the NINDS stop new enrollment, and the NIH issued a clinical alert. All patients will continue to be followed for two years to determine the long term effects of both interventions.

SAMMPRIS is the first stroke prevention trial to compare intracranial stenting with medical therapy and to incorporate intensive medical management into the study design. This includes a daily dosage of 325 milligrams of aspirin; 75 milligrams a day of clopidogrel, a medication used to prevent blood clots, for 90 days after enrollment; and aggressive management of key stroke risk factors — high blood pressure and high levels of low density lipoprotein (LDL), the unhealthy form of cholesterol. All patients also participated in a lifestyle modification program which focused on quitting smoking, increasing exercise, and controlling diabetes and cholesterol.

In a previous NIH trial, stroke patients with criteria similar to those enrolled in SAMMPRIS were treated with less intensive medical management. Their comparable 30-day and one year rates were 10.7 percent and 25 percent, respectively. The investigators note that comparisons with historical controls have limitations, but the much lower event rates in the medical group in SAMMPRIS suggest that the intensive medical management was effective in lowering the stroke risk.

Marc Chimowitz, M.B.Ch.B., of the department of neurosciences at the Medical University of South Carolina in Charleston, and first author of the NEJM article, said:

The SAMMPRIS study results have immediate implications for clinical practice. Stroke patients with recent symptoms and intracranial arterial blockage of 70 percent or greater should be treated with aggressive medical therapy alone that follows the regimen used in this trial as closely as possible.

Patients in the study were between 30 and 80 years old and had experienced a recent transient ischemic attack, a type of stroke that resolves within 24 hours, or another type of non-disabling stroke, which was caused by a large degree of stenosis in a cerebral artery.

References

1. Chimowitz et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. Epub 2011 Sep 7.
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Source: NIH News

Walter Koroshetz, M.D., deputy director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS), said:

There are many traumatic brain injury studies whose value to scientific research and clinical care could be greatly enhanced by transforming the data into a common, easily available format.

In the United States, about 1.7 million people sustain traumatic brain injuries each year from common causes such as falls and auto accidents. In addition, American Service members serving in Iraq, Afghanistan and other parts of the world face unique risks of traumatic brain injury from routine military operations, enemy fire and improvised explosive devices. According to the DoD, in the past 12 years, more than 200,000 service members deployed worldwide have been diagnosed with traumatic brain injury, adding to the urgent need for preventive methods and treatments. Total costs of traumatic brain injury in the U.S., including medical care, lost wages and other expenses, exceed $60 billion.

Colonel Dallas Hack, director of the U.S. Army Combat Casualty Research Program and joint chairperson for the Defense Health Program, said:

Despite the great burden of neurotrauma incidence, developing objective diagnostics and treatments has proven especially challenging for the medical community. Only by combining efforts through initiatives such as the FITBIR database can we hope to make major progress in this field.

Despite improved surgeries and rehabilitation techniques for people with brain injuries, treatments remain limited. Cases of traumatic brain injury are highly variable, involving different causes, locations within the brain and different kinds of damage to brain tissue. Such variability makes it difficult for clinicians to treat patients, predict long-term outcomes and investigate new therapies. Also, studies often report different kinds of data on patients, obtained through various tests and measures, further impeding comparison of data across studies. The FITBIR database will address these challenges by collecting uniform and high-quality data on traumatic brain injury, including brain imaging scans and neurological test results. The data will be obtained with informed consent and stripped of any patient-identifying information.

Matthew McAuliffe, Ph.D., co-director of the FITBIR database and a member of NIH’s Center for Information Technology (CIT), said:

Uniform data makes it much easier to compare intervention results across a broad range of studies, providing innovative and unique insights that are not possible from a single study. This is part of a larger effort by the government to make taxpayer-funded research more broadly available and usable.

The database is expected to aid in the development of:

• A system to classify different types of traumatic brain injury
• More targeted studies to determine which treatments are effective and for whom and under what conditions (comparative effectiveness research)
• Enhanced diagnostic criteria for concussions and milder injuries
• Predictive markers to identify those at risk of developing conditions that have been linked to traumatic brain injury, such as Alzheimer’s disease
• Clearer understanding of the effects of age, sex, and other medical conditions on injury and recovery
• Improved evidence-based guidelines for patient care, from the time of injury through rehabilitation

NIH CIT was chosen to build the database because of its experience and success in developing the National Database on Autism Research. Reusing the database structure is expected to save 35-50 percent of the project costs and significantly reduce the time to achieve meaningful results.

The database builds upon a larger effort to create common data elements for the study of traumatic brain injury — which are essentially definitions and guidelines about the kinds of data that should be collected, and how to collect these data in clinical studies. The Common Data Elements project emerged from a collaborative interagency effort involving over 50 American and European universities and several federal agencies, including the National Institute of Neurological Disorders and Stroke (NINDS), Defense and Veterans Brain Injury Center (DVBIC), Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE), Department of Veterans Affairs and the National Institute on Disability and Rehabilitation Research within the Department of Education.

The Defense Health Program, through agreement with the U.S. Army Medical Research and Materiel Command (USAMRMC) is the lead DoD component funding the FITBIR database. The Division of Computational Bioscience within NIH CIT is building the database, and will provide ongoing system administration and hosting services once the database is complete in about two years.

The U.S. Army Medical Research and Materiel Command (USAMRMC) and NINDS will provide programmatic support and foster collaborative research to populate the database. Researchers will be given detailed information about the FITBIR database, and encouraged to participate at the time they submit proposals for new studies.

Source: NIH News