From the Director | What's New at NCATS? | Research Opportunities Volume 02 • Issue 01 • February 26, 2013

Director's Message

Christopher Austin

In the five months since I took over as NCATS director, I have visited with a wide variety of constituents who have a stake in what we do — patients, grantees, companies, and scientists and physicians across NIH and elsewhere — and it has become clear to me that many, perhaps most, do not fully understand what "translational science" is. This knowledge gap leads to mystification at best, and misconception at worst, about what NCATS is doing and will do.

It is understandable in many ways; after all, NCATS is new and was designed to fill a critical need that complements the work of the other NIH Institutes and Centers. But for NCATS to be successful, our constituents must understand our science and mission. To that end, now and in the future, I will use recent examples of NCATS' work to illustrate what translational science is and how it differs from the basic research and clinical medicine that flank it in the research ecosystem.

One key feature of translational research is this: translation must be a team sport. Many of the greatest discoveries in fundamental laboratory research, and the best care of individual patients, are brought about by individuals who specialize in particular areas of science or medicine. I personally have been privileged to do basic research and provide clinical care. However, the translational process is so multifaceted that no one person, no matter how committed or talented, can succeed alone.

I am a fan of sports analogies (apologies in advance), and I often say "fundamental research is like golf, but translation is like football." The winning team must have not only brilliant individuals but interdependent team players to score the "touchdown" of a new intervention that improves human health in a tangible way. In other words, although all the players aren't on the "field" at the same time, each of their contributions is critical for success.

This kind of teamwork recently enabled the creation of a brain-computer-interface technology that allows paralyzed patients to move a robotic arm using only their thoughts. This remarkable work, published in The Lancet, featured on CBS' 60 Minutes and highlighted in this e-newsletter, was possible only because of the contributions of many members of a diverse research team. The collaboration relied on help from four federal agencies — NIH, the Department of Defense, the Department of Veterans Affairs, and the U.S. Food and Drug Administration (FDA) — along with support by a private foundation, a private company and two academic research centers including the University of Pittsburgh, funded in part by NCATS' Clinical and Translational Science Awards program.

In another great example of teamwork, NIH launched a clinical trial last month to test a treatment for a devastating childhood neurological disorder called Niemann-Pick disease type C. This project, also featured in this issue, moved from the laboratory to the clinic swiftly due to a collaboration of researchers in 10 different disciplines, from genetics to neurosurgery, and from four NIH Institutes and Centers, three academic institutions, several patient-oriented nonprofits and family support groups, and a pharmaceutical company. Scientists from NCATS' Therapeutics for Rare and Neglected Diseases program contributed to and coordinated the team's work.

Simultaneously, NCATS-supported research teams are creating entirely new ways to make the therapeutic development process faster, cheaper and more accurate. For example, NCATS' Tissue Chip program has partnered with the Defense Advanced Research Projects Agency and the FDA to develop microfluidic systems using 3-D human tissues that more accurately will predict potential toxicities of new drugs, thus addressing one of the primary reasons that drugs fail in development.

Finally, one of the best examples of teamwork is Rare Disease Day, a global observance on Feb. 28, 2013, with events here at NCATS and in numerous countries. All will focus on raising awareness of rare diseases and their impact on the lives of patients and families worldwide. Keep reading to learn more about what NIH has planned for later this week.

These are just some of the examples of NCATS' ongoing efforts. In each case, we have sought not only to catalyze collaborative development of new interventions, but also to establish new technologies and paradigms that can be implemented broadly to improve the efficiency of the translational process for all.

I look forward to sharing more of NCATS' translational science achievements with you as we continue to evolve. Since our mission is fundamentally collaborative, NCATS also will be highlighting ways we can hear from you and how you and your organization can get involved. I look forward to working with all of our partners as we continue to re-engineer translational science to deliver life-saving interventions more quickly to more people.


Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences

What's New at NCATS?

Austin Leads First Council Meeting as NCATS Director

Pitt Researchers Work to Restore Function in Paralysis Patients

TRND Research Leads to NIH Trial to Test Drug for Niemann-Pick Disease Type C1

NCATS Research Team Identifies Possible Treatment for Niemann-Pick Disease Type C1

ORDR Director Receives Award for Rare Disease Work

NIH Hosts Sixth Annual Rare Disease Day

New Compound Suppresses Herpes Virus Infection

NCATS Leaders Hold First Policy Workshop

30th Anniversary of the Orphan Drug Act

NCATS in the News

Christopher Austin speaks to NCATS advisory council.

Austin Leads First Council Meeting as NCATS Director

On Jan. 23, 2013, NCATS Director Christopher P. Austin, M.D., led his first joint meeting of the NCATS Advisory Council and Cures Acceleration Network (CAN) Review Board on the NIH campus in Bethesda, Maryland. Council and CAN Review Board members provide Austin with guidance and direction on NCATS' initiatives, programs and policies.

The word catalyze is part of the NCATS mission, Austin said, and NCATS is like a catalyst in its truest sense. The Center approaches problems in a unique way by bringing together other organizations to tackle common problems in a collaborative and "disease-agnostic" way that no one organization could accomplish on its own.

In his director's report, Austin provided a brief summary of what the Center has accomplished in the last three months, shared brief budget and staff updates, and highlighted several research advances.

Read the full feature to learn more and watch the archived videocast.

Jan Scheuermann and robot arm

Pitt Researchers Work to Restore Function in Paralysis Patients

Five years ago, a multidisciplinary team of researchers at the University of Pittsburgh (Pitt) and its medical center set out to tackle an important translational research goal: Restoring function for those who can't move. Now, for the first time, breakthrough brain-computer-interface research published in Lancet in December 2012 provides hope to nearly 6 million paralyzed individuals and another 1.7 million amputees nationwide.

The collaboration relied on help from four federal agencies — NIH, the Department of Defense, the Department of Veterans Affairs, and the Food and Drug Administration — along with support by a private foundation, two academic research centers and a private company. Supporting such teams to overcome roadblocks in the translational research process and turn basic discoveries into tangible health improvements is exactly what NCATS strives to accomplish.

"The problems don't end when you build a robotic arm or better computer access," explained Michael Boninger, M.D., professor and chair of the Department of Physical Medicine and Rehabilitation in the Pitt School of Medicine. "The problem has always been how someone with limited ability can control the device." Boninger and his co-investigator, Andrew B. Schwartz, Ph.D., a Pitt neuroscientist, agreed: "If we could get the technology into humans, we could have them playing the piano," he recalled saying to Boninger at the start of the project. It was with this patient perspective in mind that the team set out to make the technology work.

From the beginning, the technology was made possible by the Pitt Clinical and Translational Science Institute (CTSI), supported by NCATS' Clinical and Translational Science Awards (CTSA) program. "There is a really collaborative group of researchers at Pitt," Boninger said. "It's a critical mass. And then there's the structure that supported all of that: the CTSI."

The Pitt CTSI, which is one of about 60 CTSA-funded academic research centers dedicated to strengthening the entire spectrum of translational research, facilitated this work by providing training, regulatory expertise and pilot research support.

Read the full feature.

NPC researchers

TRND Research Leads to NIH Trial to Test Drug for Niemann-Pick Disease Type C1

Niemann-Pick disease type C1 is a rare, inherited disease characterized by progressive impairment of motor and intellectual functions in early childhood. Life expectancy often does not exceed an individual's teenage years. To date, the disease is incurable, and no drugs approved by the Food and Drug Administration are available to treat it. In 2009, the NIH Therapeutics for Rare and Neglected Diseases (TRND) program, which is led now by NCATS, chose to repurpose chemical substance called cyclodextrin, normally used as an inactive ingredient in certain formulated drug products, as a potential therapeutic for Niemann-Pick type C1.

Today, a promising new treatment is on the horizon. On Jan. 23, 2013, NIH initiated a Phase I clinical trial to evaluate the safety and effectiveness of cyclodextrin as a potential therapy for Niemann-Pick type C1. This progress is the result of the collaborative efforts of an award-winning, multidisciplinary team of experts from NCATS, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, and the National Human Genome Research Institute; Janssen Research & Development, LLC; Washington University in St. Louis School of Medicine; Albert Einstein School of Medicine, New York City; and University of Pennsylvania, Philadelphia.

Read the full story to learn more, or read a related story on another potential treatment for Niemann-Pick type C1.

From left to right: a healthy control cell; an NPC cell; an NPC cell treated with delta-tocopherol; and NPC cell treated with alpha-tocopherol.

NCATS Research Team Identifies Possible Treatment for Niemann-Pick Disease Type C1

Translational research is a team sport. To help streamline the scientific process, NCATS facilitates team-based collaborations among researchers who have various areas of expertise.

One such collaboration includes government, academic scientists, the pharmaceutical industry and patient support groups dedicated to finding potential treatments for a rare disease known as Niemann-Pick type C1. The disease causes lipids such as cholesterol to accumulate primarily in the cells of the brain, impairing movement and leading to seizures, dementia and slurred speech, among other symptoms. The majority of patients die in their teenage years.

The Niemann-Pick type C1 research team, which includes scientists from the NCATS Division of Pre-Clinical Innovation, recently showed that patient skin cells treated with a form of vitamin E, called delta-tocopherol, had lower accumulation of cholesterol. The team's findings, published in the Nov. 16 issue of the Journal of Biological Chemistry, represent another potential ingredient in a treatment cocktail for Niemann-Pick type C1.

"The Niemann-Pick type C1 research collaboration is a great illustration of the NCATS approach, which combines individual initiative and teamwork to deliver results that no one group can do alone," said Christopher Austin, M.D., director of NCATS.

Learn more about this collaborative effort, or read a related story about a new NIH clinical trial to test another potential treatment for Niemann-Pick type C1.

Michael Astrue and Stephen Groft

ORDR Director Receives Award for Rare Disease Work

Stephen Groft, Pharm.D., director of NCATS' Office of Rare Diseases Research, received the Social Security Administration (SSA) Commissioner's Appreciation Award at a commemorative Capitol Hill event in December 2012 for his work to assist rare disease patients who seek disability benefits.

Groft received the honor "in recognition of support and interagency cooperation to advance SSA's Compassionate Allowance Initiative." Compassionate allowances are a way to quickly identify certain diseases and medical conditions that qualify under the listing of impairments based on minimal objective medical information. SSA uses this system to provide benefits quickly to applicants whose medical conditions are so serious that they obviously meet disability standards, expediting the application process and enabling patients and their families to better address some of the financial challenges associated with their conditions.

"We assisted in identifying rare and genetic diseases that could qualify," Groft said. "So if you have one of these diseases, you would be eligible to receive SSA benefits." In addition, ORDR played an active role in planning and participating in the public outreach hearings for rare diseases that help determine which compassionate allowances are selected.

On Dec. 6, 2012, Groft was honored with several others during the event in Washington, D.C. The event commemorated the milestone of reaching 200 compassionate allowances conditions, many of which are rare diseases. SSA added 35 new conditions in 2012.

Learn more about this program.

Rare Disease Day 2013, February 28 and March 1

NIH Hosts Sixth Annual Rare Disease Day

Rare Disease Day is an annual international event designed to raise public awareness about the estimated 7,000 rare diseases that affect people worldwide. To commemorate Rare Disease Day, NIH is sponsoring a free two-day event for federal agencies, patient advocacy groups and those in the rare disease research community. The event is scheduled to take place from 8:30 a.m. to 5:15 p.m. on Thursday, Feb. 28, and from 8:30 a.m. to 3:30 p.m. on Friday, Mar. 1, in the Natcher Auditorium in Building 45, on the NIH campus in Bethesda, Maryland.

This year's event is organized by NCATS' Office of Rare Diseases Research and the NIH Clinical Center and will include participants from several other NIH Institutes and Centers, the Food and Drug Administration's Office of Orphan Product Development and Rare Disease Program at the Center for Drug Evaluation and Research, the National Organization for Rare Disorders, Genetic Alliance, and many other federal and nonprofit organizations.

NCATS Director Christopher P. Austin, M.D., kicks off the first day with opening remarks, followed by several presentations and discussion sessions about rare diseases efforts at partnering federal agencies. The first day closes with a screening of the Kauffman Foundation's documentary, Here. Us. Now. A Family's Fight to Bring Medical Innovation Home. The film chronicles a family's quest to find a treatment for a rare progressive neurological disease called Niemann-Pick disease type C.

NIH Clinical Center Director John Gallin, M.D., leads the second day, which focuses on NIH's efforts in rare diseases research. Rare diseases advocates also will share patient information and how they support patients and families. Both days highlight posters and exhibits. And in association with the Global Genes Project, all participants are encouraged to wear their favorite pair of jeans.

Visit NIH's event page to see the current agenda. Register now to reserve your spot at this free special event; space is limited. The event also will be available via videocast on Feb. 28 and on March 1. Contact ORDR's David J. Eckstein for questions about posters and exhibits. For logistical questions, contact ORDR.

Now in its sixth year, Rare Disease Day was established to share the challenges encountered by those affected with rare diseases, highlight the importance of research in developing diagnostics and treatments, and communicate the impact of these diseases on patients' lives. Held throughout the world, the event aims to:

See all of the Rare Disease Day events taking place this month in the United States and those across the world.

New Compound Suppresses Herpes Virus Infection

A team of scientists from NCATS' Division of Pre-Clinical Innovation (DPI) and the Laboratory of Viral Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a drug that blocks early-stage herpes simplex virus (HSV) infections in cultured cells and prevents reactivation of latent virus in mice. Importantly, the drug also prevents infection by another member of the herpes family, human cytomegalovirus (hCMV). 

Although currently available drugs represent a significant advance, they target later stages of infection, do not effectively prevent viral reactivation, and are ineffective against drug-resistant forms of the virus. hCMV is a complicating factor in organ transplants as well as the leading viral cause of birth defects. HSV continues to be the leading viral cause of blindness in the United States. A major priority of infectious disease researchers is to develop drugs that stop herpes infections at early stages.

The study was published in the Jan. 9, 2013, issue of Science Translational Medicine. The NIAID scientists, led by Thomas M. Kristie, Ph.D., showed that LSD1 and JMJD2, types of host enzymes called histone demethylases, activate early genetic events in HSV infection. Depleting cells of these proteins suppressed viral infection. The scientists surmised that chemically inhibiting the enzymes would achieve similar results.

To find a compound that could inhibit JMJD2 histone demethylases, DPI scientists and project co-leaders David Maloney, Ph.D., Anton Simeonov, Ph.D., and Ajit Jadhav developed a high-throughput assay that screened for candidates in DPI's collection of small molecules. They identified the inhibitor ML324, which the team optimized using medicinal chemistry techniques. ML324 suppressed both HSV-1 and hCMV infection in cultured cells. Importantly, ML324 also blocked reactivation of latent HSV-1 in infected mice.

"This project was a true collaboration that took the knowledge and ideas of all involved to make this significant advance," said Jadhav, chief of DPI's Probe Development Branch. "It is a wonderful example of how NCATS can work with other NIH Institutes and Centers to make important advances in translational research regardless of the disease."

Compounds like ML324 represent a new type of antiviral that targets host enzymes that modulate viral gene expression. "Because many related DNA viruses are regulated by similar mechanisms, this study demonstrates the immense potential for targeting these components in the development of novel, broad-spectrum antivirals," Kristie said. "The collaboration between the two groups with distinct expertise was essential for demonstrating this concept," he added. Scientists are also working to develop inhibitors that target similar host enzymes to treat cancer and other diseases.

NCATS Leaders Hold First Policy Workshop

On Dec. 11, 2012, NCATS partnered with stakeholders to prioritize key issues and specific policy goals in four key translational research areas at the Center's first policy workshop. Thought leaders in the federal, regulatory, academic, nonprofit and private sectors joined NCATS for a one-day workshop designed to provide advice to NCATS leadership on proactively building a solid policy research and analysis agenda within the Center's mission. Held at the Universities at Shady Grove in Rockville, Maryland, the meeting's ultimate goal was to expand the understanding of relevant policy issues to overcome hurdles that slow the development of effective treatments and cures.

Morning discussion sessions focused on the four areas of informing regulatory science, navigating intellectual property challenges, streamlining clinical research and forming effective strategic alliances. They also allowed participants to identify translational barriers that could benefit from policy research and analysis. During these sessions, experts with successful high-impact policy programs shared case studies that were followed by panel discussions.

In the afternoon, the group debriefed and developed strategies for priority setting. Eight cross-cutting themes emerged.

Members of the Office of Rare Diseases Research and the Therapeutics for Rare and Neglected Diseases program.

30th Anniversary of the Orphan Drug Act

On Jan. 7, 2013, the Food and Drug Administration (FDA) celebrated the 30th anniversary of the Orphan Drug Act in Silver Spring, Maryland. The commemorative event honored 30 heroes for their efforts in advocating and advancing treatments for rare diseases. Two honorees were NCATS' Office of Rare Diseases Research (ORDR) and the Therapeutics for Rare and Neglected Diseases (TRND) program.

ORDR was selected for "advancing rare disease information, collaboration and research." The TRND program was chosen for "stimulating drug discovery and collaborative pre-clinical development for rare disease drugs." To honor these accomplishments, the FDA is producing posters to recognize each hero and will display them at its White Oak campus.

The Orphan Drug Act, which became law in 1983, was designed to facilitate the development and commercialization of drugs to treat rare diseases. "The success of the Orphan Drug Act has been the result of the collaborative multidisciplinary efforts to recognize and meet the needs of its partners," said Stephen Groft, Pharm.D., ORDR director and a speaker at the event. He recognized partners in the pharmaceutical, biotechnology and medical device industries; academia, foundations and medical specialty societies; patients, families and advocacy groups; and branches of the federal government.

Other speakers included Gayatri Rao, M.D., J.D., director of the FDA Office of Orphan Products Development; Peter Saltonstall, president and CEO of the National Organization for Rare Disorders; and Margaret Hamburg, M.D., FDA commissioner.

For more information, read an FDA blog entry.

NCATS in the News

NCATS and its programs are in the news frequently. Below are a few examples of recent media coverage:

Be sure to visit our News & Events page to learn more about these stories and other NCATS programs in the news.

Research Opportunities and Announcements

Visit the NCATS Open Opportunities page for a complete list of funding and program announcements.

We Want to Hear from You

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