From the Director | What's New at NCATS? | Research Opportunities Volume 01 • Issue 05 • December 10, 2012

Director's Message

Christopher Austin

As I enter my third month as director, NCATS is moving boldly toward establishing a strategic vision that will transform the translational process for the benefit of science and patients. We are establishing an organization that emphasizes innovation and deliverables and relying on the power of data to develop, demonstrate and disseminate improvements in translational science.

Recently, I have been meeting with a wide spectrum of those in the research ecosystem who are important to NCATS' mission. In addition to scientists and other staff throughout NCATS, I am meeting with each of my 26 fellow NIH Institute and Center directors as well as representatives from patient advocacy organizations, biotechnology and pharmaceutical companies, foundations, and the U.S. Food and Drug Administration and other government agencies. In October, I had the opportunity to meet and exchange ideas with investigators from the Clinical and Translational Science Awards (CTSA) program during their national consortium meetings, and I've also been visiting a number of CTSA sites throughout the country.

In all of these conversations, I am seeking advice on NCATS' priorities, that is, the most urgent and pervasive roadblocks in the translation of fundamental scientific discoveries into tangible benefits for human health. Using this input, I am formulating NCATS' initial strategic priorities and directions, which are focused on making the translational research process more efficient, science-based and predictive. I have been tremendously gratified by the outpouring of goodwill, offers of collaboration, and ideas, and I look forward to continuing these conversations.

As we move forward, NCATS continues to accomplish much, and some of these achievements are highlighted below. For example, last week, we announced several new awards and a new solicitation from NCATS' Bridging Interventional Development Gaps (BrIDGs) program.  And, during the NIH Research Festival, NCATS showcased its science advances in the areas of cancer, rare diseases, medicinal chemistry and technology development. Additionally, NCATS scientists have discovered a new method to better identify drug candidates. I hope you'll enjoy these and all of the other features in this issue.

Thank you for your continued support and interest in NCATS!  I wish you the very best for the holiday season.

Sincerely,

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

What's New at NCATS?

NIH BrIDGs Program Helps Overcome Research Roadblocks

NCATS Researchers Create New Method to Help Scientists Better Identify Drug Candidates

CTSA Training Enables Research on the Effects of Antibiotics on Body Fat

Patients with Rare Muscle Disorder Benefit from Repurposed Heart Drug

NCATS Robot Becomes Calendar Model

NCATS Scientists Featured at NIH Research Festival

IOM Committee Holds First CTSA Program Review Meeting, Plans for More

Frontiers in Science Event Gives Kids Hands-On Lab Experience

NCATS in the News

Technician working in a lab

NIH BrIDGs Program Helps Overcome Research Roadblocks

Potential new treatments for a variety of cancers, spinal cord injury, and a rare disease that can lead to kidney failure are targets of a program that provides eligible scientists with no-cost access to NIH therapeutic development contractor resources.

Often, researchers apply to this NIH program, called Bridging Interventional Development Gaps (BrIDGs), because they lack private resources or they have hit a roadblock and need additional expertise. Rather than funding successful applicants directly, BrIDGs enables NIH contractors to provide pre-clinical services — such as toxicology studies — for therapeutic projects that have demonstrated efficacy in a disease model.

BrIDGs, formerly known as NIH Rapid Access to Interventional Development, is supported by the NIH Common Fund. At times, NIH Institutes and Centers contribute additional funding to support projects relevant to their missions. NCATS leads the eight-year-old program.

For the majority of projects, the goal is to enable the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration. Human clinical trials using an investigational new drug may commence within 30 days of the submission of an IND for that drug unless the FDA informs the sponsor that the IND is subject to a clinical hold. To date, BrIDGs has generated data to support 12 INDs submitted to the FDA and one clinical trial application to Health Canada. Twelve of the 13 projects have been evaluated in clinical trials. Three BrIDGs-supported therapeutic agents have gone as far as Phase II human clinical trials, in which researchers give an experimental therapy to a group of patients to evaluate the effectiveness and safety of the treatment. Third-party investors have licensed six agents during or after their development by BrIDGs.

"I am excited by the high success rate of this program," said Christopher P. Austin, M.D., director of NCATS. "As its name implies, the program bridges the gap between a basic discovery and clinical testing by providing the expertise needed to perform crucial pre-clinical studies, often breathing new life into projects that otherwise may never reach patients."

Read the full news release for details about the new solicitation and new projects, and visit the BrIDGs Projects page for a list of active projects.

Hand holding a pipette with orange liquid over an assay plate

NCATS Researchers Create New Method to Help Scientists Better Identify Drug Candidates

In the past few years, researchers have discovered that the use of reporter genes, a powerful technique widely used in drug discovery screening, can produce misleading results and lead to wasted effort and inefficiency in the drug discovery process. Now, researchers from NCATS have designed a novel method that increases the odds of identifying candidate compounds with true activity against biological or disease targets. Scientists use these compounds as molecular tools to understand disease and as starting points for developing new therapeutics. Details of the methodology are described in a correspondence published in the October issue of Nature Methods.

Reporter genes produce proteins that act as light-generating (e.g., luminescent or fluorescent) sentinels when a chemical compound produces an effect in a testing system (an "assay") designed to represent a biological or disease process. Such assays enable researchers to examine hundreds of thousands of compounds using robotic high-throughput screening systems, such as those in the NCATS Division of Pre-Clinical Innovation (DPI). Typically, scientists use a single reporter gene for screening; however, because chemical compounds may interact with the reporter gene proteins themselves, rather than with the intended target, these tests can be misleading.

Compounds affecting the reporter may inhibit its activity or alternatively may bind to and stabilize it, increasing its abundance and activity in the cell. In either case, a researcher may see a strong effect of the compound in the assay and erroneously conclude that this indicates action on the biological pathway or target of interest. But, it is more a case of the reporter doing "false advertising," leading the researcher to conduct further testing and development, and even clinical trials, that ultimately fail because the compound only has activity on the reporter, not the disease target.

"The mission of NCATS is to develop, demonstrate and disseminate technologies and paradigms that improve the accuracy, efficiency and predictability of the translational process," said Christopher P. Austin, M.D., NCATS director. "This innovative reporter gene system is a great example of such a platform technology, which will help researchers worldwide in achieving more reliable results early in the translational process and avoiding failure at later stages."

Read the full story.

Ilseung Cho

CTSA Training Enables Research on the Effects of Antibiotics on Body Fat

A core component of NCATS' Clinical and Translational Science Awards (CTSA) program is training, cultivating and sustaining future leaders in the biomedical research workforce. New York University (NYU) School of Medicine's Ilseung Cho, M.D., M.S., attests that his school's CTSA support has made crucial and ongoing contributions to his professional growth and achievements.

Cho began studying how antibiotics alter the community of bacteria living in the guts of mice as part of his thesis for a CTSA-funded master's degree in clinical investigation, a program open to researchers who have completed residency training in a clinical department at NYU. The research, which began during Cho's last year of his gastroenterology fellowship, has continued through his transition into a faculty member at NYU.

Researchers have long known that feeding low doses of antibiotics to farm animals makes them grow faster and up to 15 percent larger, but the mechanism behind the effects has remained unclear. Now, thanks to a study supported by a CTSA training grant and by the NYU Clinical and Translational Science Institute (CTSI), Cho and his colleagues have shed light on several of the changes that occur in those animals. Their success hinged on the connections and ideas generated in the setting of mentoring meetings as part of the CTSA training program.

Read more about Cho's research and career path.

Patients with Rare Muscle Disorder Benefit from Repurposed Heart Drug

Patients with nondystrophic myotonia, a rare genetic muscle disorder, often have problems with debilitating muscle stiffness, fatigue, and sometimes even episodes of paralysis. Now, these patients have new help:  a drug called mexiletine, normally used to treat heart disorders. With assistance from NIH's Rare Diseases Clinical Research Network (RDCRN) and Clinical and Translational Science Awards (CTSA) program, researchers at seven institutions in four countries collaborated to demonstrate in a clinical trial that the heart drug is effective in treating patients with this rare disease.

In a study published in JAMA in October 2012, a research team led by Jeffrey Statland, M.D., a neurologist at the University of Rochester Medical Center, found that mexiletine significantly improved patient-reported muscle stiffness. Jaya Trivedi, M.D., at UT Southwestern Medical Center in Dallas, one of the authors of the study, said, "Nondystrophic myotonia is not as debilitating as some forms of muscular dystrophy that lead to a wheelchair-confined state, but the symptoms it produces significantly impair patients' daily living activities." Symptoms may be triggered by cold, exercise or other exposures. Last summer, she said, she saw a 14-year-old boy with the disease who plays baseball, but if he isn't warmed up, he can't even run to first base.

Rare diseases such as this one are a focus of the RDCRN's Consortium for Clinical Investigation of Neurologic Channelopathies (CINCH). The RDCRN, which is managed by NCATS' Office of Rare Diseases Research (ORDR) and supported by several NIH Institutes and Centers, facilitates collaboration among experts to explore the natural history, epidemiology, diagnosis and treatment of nearly 100 rare diseases. The RDCRN consists of a Data Management and Coordinating Center and 17 distinct clinical research consortia ? each of which studies a minimum of three related diseases. For each disease, consortia members work together to implement a natural history study that describes the disease and its symptoms over time, then they carry out other studies such as drug or other treatment trials.

CINCH researchers already had completed a natural history study of nondystrophic myotonia, and the next step was a study of mexiletine, a generic drug normally used to treat cardiac arrhythmias or seriously irregular heartbeats. Since the 1980s, doctors have prescribed mexiletine off-label for nondystrophic myotonia, and it seemed to help some patients. But since the disease is so uncommon, no one had been able to study the drug in enough patients to find out if it actually worked in a large study.

Through the RDCRN, researchers were able to find the 60 patients needed for the evaluation. The RDCRN has centers in multiple locations around the world and provides tools and resources to support a broad, international collaboration.

Read the full feature.

Tox21 robot

NCATS Robot Becomes Calendar Model

NCATS' ultra-high-throughput screening robotic system will be featured in the 2013 calendar from the Federal Laboratory Consortium (FLC) for Technology Transfer. The robot, located in the NCATS Division of Pre-Clinical Innovation, is known for its glowing yellow disposition.

The FLC calendar showcases technology used for research and development in federal laboratories. More than 10,000 people, including members of Congress, scientists and technology transfer professionals, receive the calendar. Although no one knows in which month the robot will appear, the consensus at NCATS is that the robot's glowing yellow skin would be a welcome site during the darker winter months. The calendar will appear in the FLC Library once it is printed. Request your copy by sending an e-mail to orders@federallabs.org.

NIH Research Festival

NCATS Scientists Featured at NIH Research Festival

NCATS researchers and staff highlighted many of the Center's recent science advances and new initiatives at the 26th Annual NIH Research Festival Oct. 9–12 on the NIH campus in Bethesda, Maryland. This year's festival theme was "The NIH at 125: Today's Discoveries, Tomorrow's Cures," and translation was a prominent topic of discussion.

Topics such as "translation research in addiction, stress and anxiety" and "how to put the 'translational' into your research" were two of many featured presentations. Experts from NCATS' Office of Rare Diseases Research (ORDR) and NCATS' Division of Pre-Clinical Innovation (DPI) chaired panel discussions; served as key presenters; and showcased NCATS science in the areas of cancer research, rare diseases, chemistry advances and core technologies during poster presentations.

ORDR Director Steven Groft, Pharm.D., and P.J. Brooks, Ph.D., an ORDR program director, co-chaired a presentation about the NIH Clinical Center's Bedside-to-Bench Program, which funds intramural and extramural collaborative research teams seeking to translate basic scientific findings into therapeutic interventions for patients and to increase understanding of important disease processes. Specifically, Groft and Brooks discussed the benefits of these collaborative research teams related to rare disease research. DPI scientist Marc Ferrer, Ph.D., discussed the use of stem-cell-derived cellular disease models for drug screening.

Read more about NCATS' presence at the festival, and see detailed abstracts about each of the Center's presented posters. 

IOM Committee Holds First CTSA Program Review Meeting, Plans for More

As reported in our September issue, NIH has commissioned the Institute of Medicine (IOM) to assemble an ad hoc expert committee to evaluate NCATS' Clinical and Translational Science Awards (CTSA) program. The committee met for the first time on Oct. 29, 2012, via a teleconference rather than in person, due to Hurricane Sandy. The agenda featured presentations about NCATS and the CTSA program to date as well as input from leaders at other NIH Institutes and Centers.

IOM committee members also are reviewing existing evaluations and are seeking additional information through outreach to stakeholders. Two more public meetings are planned for Dec. 12, 2012, and Jan. 24, 2013, in the Washington, D.C., area. In June 2013, the committee will release a report with recommendations.

For more information, visit the IOM website.

Rajan Pragani, Ph.D., and students

Frontiers in Science Event Gives Kids Hands-On Lab Experience

Real-world, hands-on laboratory experiences can spark students' scientific curiosity and propel them along a career path to pursue science and medicine. To this end, NCATS joined 20 local biotechnology, research, university and health care organizations on Oct. 26, 2012, for Frontiers in Science and Medicine Day. This fourth annual event featured lab tours and interactive science activities for more than 500 Montgomery County, Maryland, public school children.

"We have a responsibility to teach and inspire the next generation of researchers," said Anton Simeonov, Ph.D.,chief of the Chemical Genomics Branch in the NCATS Division of Pre-Clinical Innovation (DPI).

NCATS opened the doors of its DPI laboratories in Rockville, Maryland, to seventh-graders from two local middle schools to showcase its high-powered robotic drug screening equipment and other research concentrations. Chemistry lab scientists demonstrated several experiments, including the chemical interaction of baking soda and vinegar. Other NCATS researchers illustrated how a simple chemical reaction can convert a liquid to a solid by teaching students how to make slime using glue and watered-down laundry detergent.

"Demonstrations like these made me enjoy science and sparked my imagination when I was growing up," said Andrew Rosenthal, Ph.D., a postdoctoral fellow in DPI's Probe Development Branch. "So, I always volunteer for events like this to inspire the next generation of students."

Learn more about NCATS' research programs.

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

We welcome your feedback to ensure that we are meeting the needs of all of our stakeholders. Please e-mail us directly at info@ncats.nih.gov, follow us on Facebook and Twitter, view our YouTube channel, and join the NCATS e-mail list for other Center announcements.

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