As many as 25 million people in the United States are suffering from one of more than 6,500 rare diseases. Although each rare disease affects fewer than 200,000 Americans, in total, these illnesses affect a large part of our population. With NCATS' emphasis on identifying commonalities among diseases as a route to accelerating the translational process, we are tackling the problems of rare disorders in an integrated way.
Obstacles to rare disease treatments include difficulties in diagnosis, widely dispersed patients and scientific experts, and the high perceived risk of developing such treatments. NCATS' rare disease initiatives, including the Office of Rare Diseases Research (ORDR) and Therapeutics for Rare and Neglected Diseases (TRND) program, are directly addressing these obstacles, and thus, making rare disease translational research easier and more efficient for all.
Two events this month have caused me to reflect on the enormous progress made in rare diseases research over the past several decades. First, ORDR Director Stephen C. Groft, Pharm.D., retired on February 8 from a position he held for the past 25 years, providing visionary leadership in rare diseases research and bringing hope and progress to patients across the globe. On February 28, NIH will celebrate Rare Disease Day, an annual event established to raise public awareness about rare diseases and highlight advances in the field.
In this issue of the e-newsletter, you can read about Steve's remarkable work and legacy. If you are in the Washington, D.C., area, please join us in honoring him and the entire rare diseases research community at Rare Disease Day at NIH. This year's event will highlight the latest research, offer NIH Clinical Center tours, and feature scientific posters and exhibits from NCATS and many other agencies and organizations.
Another story in this e-newsletter highlights the development of a groundbreaking combination drug screening platform by a team of NCATS and National Cancer Institute scientists. This technology platform quickly identifies drug combinations with the most potential to help patients, and promises to speed translation for many diseases, both rare and common. Also, keep reading to learn about a new collaboration that will open a frontier in the technology for printing 3-D tissues, which could be used for testing potential drugs.
Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences
To treat diseases such as cancer, tuberculosis and brain disorders, doctors often administer more than just one drug — an approach known as combination therapy. Despite some success with this approach, clinicians often must make decisions based on trial and error. With thousands of approved and investigational drugs, there are millions of possible drug pairings and dose variations.
To find a better way to sort through all of these combinations, collaborators from NCATS and the National Cancer Institute recently tested a sophisticated drug screening platform, designed to speed the drug combination research process.
In the Jan. 27, 2014, early edition of the journal Proceedings of the National Academy of Sciences, the team published the results of a collaborative study that demonstrates how the platform quickly can narrow down a long list of potential drug combinations to find those with the most potential to help patients. Investigators chose a difficult-to-treat variety of diffuse large B-cell lymphoma, a type of blood cancer, as the model for the study.
"NCATS is unique in its dedication to improving the process of translational research," said NCATS Director Christopher P. Austin, M.D., also an author on the paper. "This platform promises to take years off the process of testing new combination treatments for cancer and countless other diseases."
Read the feature story to learn more.
Stephen C. Groft, Pharm.D., helped bring renewed hope and a collective voice to thousands of rare disease patients and their families. A public servant for more than four decades and a tireless advocate for rare diseases research, Groft is recognized by many as a luminary and true champion of rare diseases research.
On Feb. 8, 2014, Groft retired from his current position as director of NCATS' Office of Rare Diseases Research (ORDR). He leaves a 30-year legacy of advancing rare diseases research and improving the lives of patients with these conditions. Pamela M. McInnes, D.D.S., M.Sc.(Dent.), NCATS deputy director, is serving as acting director of ORDR during the search for a new director.
"The creation of NCATS was in many ways a validation of Steve's work over the past 30 years," said NCATS Director Christopher P. Austin, M.D. "Rare diseases are no longer a curiosity on the periphery of the biomedical research enterprise. They now are central to the research agenda, and that is due in large part to Steve's vision, dedication and effectiveness."
Read a Web feature highlighting Groft's accomplishments to advance rare diseases research.
NCATS is seeking applicants for a new two-year postdoctoral fellowship position funded by the Alpha-1 Project, the philanthropic arm of the Alpha-1 Foundation. The selected candidate will work in NCATS' laboratories to help advance therapeutic strategies for alpha-1 antitrypsin deficiency (alpha-1). Alpha-1 is a rare genetic condition in which the body does not circulate enough of a protein that protects the lungs from damage.
Qualified applicants must hold a Ph.D. in chemical, molecular or cellular biology. Once selected, the fellow will work with drug discovery and development experts in the assay development screening technology laboratory in NCATS' Division of Pre-Clinical Innovation. He or she will receive training in assay development, screening techniques and data analysis to become equipped to lead a translational research project. Interested candidates may apply via the NIH Office of Intramural Training & Education website through May 5, 2014.
The fellowship is based on an innovative collaboration model used at NCATS to involve patient groups proactively in the design and implementation of drug discovery projects. Groups like the Alpha-1 Foundation provide in-depth knowledge and patient perspectives for specific diseases. Learn more by reading the Alpha-1 news release or view the NCATS job description.
On Dec. 20, 2013, the journal Stem Cell Research & Therapy published a special supplement that provides an overview of many of the current projects from NCATS' Tissue Chip for Drug Screening program. Stem Cells on Bioengineered Microphysiological Platforms for Disease Modeling and Drug Testing features reviews by the researchers on their progress to date in the areas of innovative cell resources and model systems. NCATS' Dan Tagle, Ph.D., who oversees the Tissue Chip program, authored a brief introduction about the program, its goals and the focus of the projects. The supplement highlights 18 projects.
Researchers in the collaborative Tissue Chip program, which is supported by NIH, the Food and Drug Administration, and the Defense Advanced Research Projects Agency, are developing 3-D "organs-on-chips" to accurately model the structure and function of the human organ systems. Once these chips are developed, researchers will be able to use them to improve the process for predicting whether new drugs will be safe in people. Read the full feature.
A new NIH–Organovo research collaboration aims to help scientists develop more reliable tools for bringing safer, more effective treatments to patients on a faster timeline. NCATS and the National Eye Institute (NEI) will work with Organovo to develop better and more clinically predictive tissue models, using its NovoGen MMX Bioprinter®. The 3-D printer will be housed in NCATS' Division of Pre-Clinical Innovation laboratory in Rockville, Maryland. With this technology, the scientists will create 3-D, architecturally accurate, functional living tissues. These 3-D human tissues have the potential to accelerate the drug discovery process, enabling treatments to be developed faster and at a lower cost.
"Our 3-D printer creates living human tissues that more closely reproduce in vivo human tissues," said Keith Murphy, Organovo's chief executive officer. "In collaboration with NIH, which has worked to highlight and address the critical need for better models that can lead to better drugs, we hope to create tissue models that give researchers a much more accurate view of how drugs will behave in human beings before those drugs ever enter clinical trials."
"Developing collaborations like this is central to NCATS' mission," said NCATS Director Christopher P. Austin, M.D. "We look forward to working with Organovo and our colleagues at NEI to develop a printable eye tissue. We also plan to develop more tissue models that complement and leverage our current Tissue Chip and compound screening programs."
Read the Organovo news release.
In the United States, a rare disease generally is considered to be one that affects fewer than 200,000 Americans, and there are more than 6,500 of these diseases. Feb. 28, 2014, marks NIH's annual celebration of Rare Disease Day, an established forum for communicating about rare diseases, the challenges encountered by those affected, and the importance of research to develop diagnostics and treatments.
Presented by the NCATS' Office of Rare Diseases Research and the NIH Clinical Center, the event will take place from 8:30 a.m. to 5:00 p.m. in Masur Auditorium, located in Building 10 on the NIH campus in Bethesda, Maryland. Attendance is free and open to the public. NIH Director Francis S. Collins, M.D., Ph.D., and NIH Clinical Center Director John I. Gallin, M.D., will provide opening remarks. NCATS Director Christopher P. Austin, M.D., will speak in the afternoon. Patients and patient advocates, health care providers, researchers, and industry representatives also will participate.
The event will feature tours, presentations, posters and exhibits from the rare diseases research community. Topics include medical devices for rare diseases, advanced imaging techniques for insight into rare genetic heart disease, the NIH cyclodextrin trial and the Undiagnosed Diseases Network. View the full agenda. Follow the event on via social media using hashtag #RDDNIH.
Partner organizations include the U.S. Food and Drug Administration, National Organization for Rare Disorders, Genetic Alliance, Global Genes Project and Uplifting Athletes.
Translational science is a team sport, so every project that NCATS scientists tackle involves collaboration with at least one partner from either government, academia, industry or nonprofit patient organizations. Working collectively is vital to establishing innovative approaches that can benefit the broad scientific and patient communities.
NCATS leaders, staff and partners published three articles in the February 2014 Current Topics in Medicinal Chemistry, a themed issue focused on collaboration.
The first article, "Playing well with others! Initiating and sustaining successful collaborations between industry, academia and government," is a free downloadable editorial by John C. McKew, Ph.D., acting director of the NCATS Division of Pre-Clinical Innovation (DPI), and Craig Thomas, Ph.D., head of DPI's chemistry technology activities. The authors highlight several collaborations that led to success despite a challenging environment of diminishing resources.
In "Leveraging public private partnerships to innovate under challenging budget times," authors Lili Portilla, M.P.A., director of NCATS' Office of Strategic Alliances, and Mark Rohrbaugh, Ph.D., director of the NIH Office of Technology Transfer, describe how new NIH and industry alliances are helping to strengthen the drug development pipeline.
The third article, "Collaborative development of 2-hydroxypropyl-?-cyclodextrin for the treatment of Niemann-Pick type C1 disease," describes one of the first projects taken on by NCATS' Therapeutics for Rare and Neglected Diseases program. Authors from NCATS and other NIH institutes and centers, academia, and the private sector explain how they overcame scientific, clinical and financial challenges to develop a therapy using cyclodextrin as a potential treatment for Niemann-Pick type C1 disease, a fatal genetic disorder. NIH researchers now are evaluating cyclodextrin in a phase I clinical trial at the NIH Clinical Center.
On Dec. 16, 2013, NCATS leaders joined officials from the Italian Ministry of Health and other leaders for a scientific roundtable discussion on rare diseases. The event, held at the Italian Embassy in Washington, D.C., culminated in a formal agreement between NCATS and the National Centre for Rare Diseases at the Istituto Superiore di Sanità of the Italian Republic to increase cooperation in the field of rare diseases research and in related training.
NCATS Director Christopher P. Austin, M.D.; Stephen C. Groft, Pharm.D., former director of the NCATS Office of Rare Diseases Research; and academic scientists, federal regulatory experts, nonprofit leaders, patient groups and business experts participated. Topics included rare diseases diagnostics and treatments, as well as the positive effects of international collaborations among professionals, patients and families.
Italian Ambassador to the United States Claudio Bisogniero called the initiative "a collaboration of the highest level," taking advantage of the support provided by both of these leading scientific institutes. "It is an important tool for opening new opportunities for collaboration."
The two organizations plan to work together to advance research efforts that reduce global health disparities. Some areas of common interest include joint research projects, workshops, training opportunities, and sharing resources such as patient registries and biorepositories. "Developing a mutual trust through agreements like this one shows that we are willing to share data, information and programs to enable advances in rare diseases research," said Groft.
The new agreement grew out of an earlier memorandum of understanding, established in 2003, that focused on research including rare diseases, HIV/AIDS, cancer and biodefense.
In its 2013 Research Highlights, NIH Research Matters featured six science advances that involved NCATS support. The year-end compilation highlighted some of the year's most interesting clinical breakthroughs, promising medical advances, and insights from basic research.
NCATS scientists collaborated with other NIH researchers to discover a new target for Parkinson's disease and to help develop a malaria vaccine candidate. In four additional projects, Clinical and Translational Science Awards helped support advances for a test for kidney rejection, medical management for stroke prevention, the human microbiome, and a technique that forms working inner ear cells.
Read more in NIH's 2013 Research Highlights.
On Jan. 26, 2014, Dorit Zuk, Ph.D., joined NCATS as director of the Office of Policy, Communications and Strategic Alliances. Zuk is overseeing the Center's policy, evaluation, reporting and communications functions. In her more than 25 years of experience, Zuk gained expertise in developing NIH extramural research policy; implementing NIH-wide strategic initiatives; and editing major scientific journals, including Cell and Molecular Cell.
"Translational science brings with it unique policy and communication challenges and opportunities for which Dorit's remarkable background and skills are ideally suited," said NCATS Director Christopher P. Austin, M.D.
Zuk previously served as the science policy advisor to Sally Rockey, Ph.D., deputy director for extramural research at NIH. In that role, she developed, coordinated, and disseminated policies and procedures for a variety of research-related issues, such as financial conflicts of interest and the biomedical research workforce.
Zuk began her NIH career in 2009 after spending a year as a Hellman Fellow for science policy at the American Academy of Arts and Sciences. Prior to that, she was an American Association for the Advancement of Science (AAAS) Science and Technology Policy Fellow in the NIH Office of Extramural Research. From 2000 to 2007, she was the scientific editor at Cell Press, serving as the deputy editor of the journal Cell from 2000 to 2002 and as the editor of Molecular Cell from 2003 to 2007.
Zuk reports to NCATS Deputy Director Pamela McInnes, D.D.S., M.Sc.(Dent.), who also began her new leadership position at NCATS in January. Learn more about these recent leadership updates.
During his director's report, Austin highlighted the Center's most recent scientific advances and outreach initiatives. He also provided updates on the NIH and Center budgets and related legislation.
"The conversation about NCATS has changed dramatically over the past year and a half, in part due to what we're doing, and in part due to what you're doing," he told Council and CAN Review Board members. "I hear very little skepticism these days about NCATS' mission, and that is an important shift."
Austin then spoke about changes NCATS is making in response to the Institute of Medicine (IOM)'s report on the Clinical and Translational Science Awards (CTSA) program. In addition, he outlined NIH leadership efforts to improve the NIH scientific review and grant funding processes.
Following the director's report, CAN Review Board Chair Freda Lewis-Hall, M.D., led a discussion on potential uses for CAN's other transaction authority. Austin presented several funding ideas, including concepts generated through the NIH Common Fund, by the IOM and by NCATS-funded investigators.
Other presenters were Office of Rare Diseases Research Director Stephen C. Groft, Pharm.D., who retired from the NIH on Feb. 8, 2014, and W. Charles Huskins, M.D., M.Sc., professor of pediatrics at Mayo Clinic. Groft provided his career-long perspective on advances in rare diseases research, and Huskins spoke about a pilot study of the Pediatric Point Person Project, a CTSA initiative to match investigators to collaborative research projects. The open session ended with the review and approval of a concept for platform delivery technologies for nucleic acid therapeutics.
View the archived videocast of the meeting to learn more.
On Feb. 28, 2014, NCATS and the NIH Clinical Center will host Rare Disease Day at NIH. This annual event features presentations, tours, posters and exhibits to highlight rare diseases research activities. Partner organizations this year include the U.S. Food and Drug Administration's Office of Orphan Products Development, National Organization for Rare Disorders and the Genetic Alliance. Attendance is free and open to the public.
Fourth AIMBE/NIH Workshop on Validation and Qualification of New In Vitro Tools and Models for the Pre-Clinical Drug Discovery Process
On March 6–7, 2014, the American Institute for Medical and Biological Engineering (AIMBE) and the National Institute of Biomedical Imaging and Bioengineering will hold the fourth in a series of workshops designed to help researchers turn new technologies into useful and meaningful tools. The event will take place in Lister Hill Auditorium on the NIH campus in Bethesda, Maryland. Event leaders will build upon their previous workshop results and recommendations to begin developing guidelines for validation and qualification of new model systems. Specific emphasis will be on systems that may augment or replace existing ones, especially animal models, in the FDA drug approval process.
On May 16, 2014, NCATS will hold a joint meeting of the NCATS Advisory Council and the CAN Review Board on the NIH campus in Bethesda, Maryland. The meeting will feature reports from NCATS Director Christopher P. Austin, M.D., and others about the Center's initiatives, policies, programs and future direction.
- The Alpha-1 Project funding PhD fellowship at NIH; applications due by April 30 • Alpha-1 Foundation • February 12, 2014
- Lumos Pharma Announces Series A Financing • Digital Journal • February 04, 2014
- Biostatistics Approach to Genetics Yields New Clues to Roots of Autism • The Rockefeller University • January 31, 2014
- $7 Million Multi-Institutional Contract Creates New York City Clinical Data Research Network • Albert Einstein College of Medicine • January 29, 2014
- High-Throughput Screening Identifies Synergistic Targets • ecancer News • January 29, 2014
- Addressing Challenges in Rare Disease Drug Development - Together: Dr. Groft of NIH on New Hope for Rare Disease Research and Treatments • PhRMA • January 27, 2014
- Profiles in Innovation: Interventionist • Biocentury This Week • January 26, 2014
- Profiles in Innovation: End Goal • Biocentury This Week • January 26, 2014
- Profiles in Innovation: Catalyst • Biocentury This Week • January 26, 2014
- Pharmacists, Electronic Health Record Use Improves Shingles Vaccination Rate Among Baby Boomers • The Ohio State University • January 17, 2014
- Move Over Holter? Heart Monitoring in the mHealth Era • NIH Director's Blog • January 16, 2014
- High-Tech Medicine: App to Improve Outcomes from Deep Brain Stimulation • Medical College of Wisconsin • January 14, 2014
- Organovo Holdings (ONVO) Enters Collaboration with Two NIH Units • StreetInsider.com • January 14, 2014
- Researchers Gain Insight into Retinal Detachment after Open Globe Injury • Massachusetts Eye and Ear • January 01, 2014
- "It's Alive!" How Tiny "Organs" on Microchips Could Replace Mice and Rats in Medical Research Labs • National Post • December 28, 2013
- EPA Releases Data on 1,800 Chemicals • Environmental Leader • December 18, 2013
NCATS researchers are seeking collaborators in the following areas:
Bridging Interventional Development Gaps (BrIDGs) Program
The BrIDGs program makes available, on a competitive basis, certain critical resources needed for the development of new therapeutic agents. The next opportunity to apply to the BrIDGs program tentatively is scheduled for January/February 2015. Visit the BrIDGs Web page for more information.
NCATS Chemical Genomics Center (NCGC)
NCGC is one of the centers in the Molecular Libraries Probe Production Centers Network (MLPCN), which is an NIH Common Fund initiative. Through the MLPCN, NCGC offers biomedical researchers access to large-scale screening capacity along with the medicinal chemistry and informatics expertise necessary to identify chemical probe molecules and to study the functions of genes, cells and biochemical pathways. For inquiries or to obtain NCGC probe molecules, contact Ajit Jadhav.
NCGC researchers also seek collaborators for assay development and high-throughput screening, chemistry and chemistry technology, automation, and informatics. Learn more.
NIH RNA Interference (RNAi) Initiative
The NIH RNAi initiative, administered by NCATS, provides state-of-the-art, high-throughput RNAi genome-wide screens for humans and mice. This resource is available only to NIH researchers. Scientists interested in performing high-throughput RNAi screens can contact Scott Martin, Ph.D., for more information.
Toxicology in the 21st Century (Tox21) Program
The Tox21 program aims to test 10,000 chemicals and evaluate their potential to cause health problems. Any investigator may propose the development of biological assays for high-throughput screening.
To suggest an assay, submit an assay nomination form to Menghang Xia, Ph.D. Proposed assays must be compatible with the high-throughput screening guidelines as described in the assay guidance criteria.