2017 Director’s Messages

Select a 2017 message from the list below:

Jan. 26, 2017: A New Year’s Resolution for Accelerating Progress in Translational Science

Readers of this column will know that one of my favorite sayings about translation is that it is a “team sport.” But as any coach knows, teamwork is just that: work. It requires intentionality, goodwill, mutual dependence and knowledge that the team can produce a result that no individual team member could accomplish alone. There is a science to teamwork just as there is to organic chemistry, and since high-functioning teams are so critical to translational success, NCATS strives to understand the general principles of productive scientific teams, and constantly innovates in models of partnership. In fact, developing, demonstrating the usefulness of, and disseminating effective translational team structures is a prominent goal in the new NCATS Strategic Plan. An advance in a potential treatment for a rare and devastating lung disease illustrates why.

Bruce Trapnell, a physician and researcher at Cincinnati Children’s Hospital Medical Center and principal investigator in the NCATS-led Rare Diseases Clinical Research Network, Rare Lung Diseases Consortium, cares for patients with autoimmune pulmonary alveolar proteinosis (aPAP) and seeks to understand and better treat the disease. In aPAP, an immune system malfunction causes proteins and lipids to pile up in the tiny gas-exchange pockets in the lungs, eventually leading to an inability to breathe. The current standard treatment, akin to internal lung-washing, is complicated and dangerous. Patients desperately need a new, more effective therapy.

Dr. Trapnell knew there was evidence that an inhaled version of a protein drug called GM-CSF might effectively treat aPAP, but he had neither the resources nor the expertise to develop the drug so that it might be tested in patients. He partnered with NCATS through its Therapeutics for Rare and Neglected Diseases program. NCATS provided the drug development know-how, resources and regulatory knowledge needed to complement Dr. Trapnell’s disease expertise. However, at that point, the team did not have access to the drug, which belongs to the biopharmaceutical company Sanofi Genzyme, which markets it in injectable form for other diseases. Enter the NCATS Office of Strategic Alliances, which brokered an agreement among Sanofi Genzyme, NCATS and Cincinnati Children’s to enable production and testing of an inhaled version of GM-CSF for testing in aPAP patients. The three partners each had critical expertise and resources which complemented the others, and together they were able to rapidly complete the work required to successfully develop inhaled GM-CSF for a clinical trial. However, another roadblock loomed since the team lacked the study support needed for the clinical trial. So they expanded their team, turning again to NCATS through its Clinical and Translational Science Awards (CTSA) Program. With CTSA Program support, including the recently launched institutional review board (IRB) reliance platform, Trapnell and his colleagues will carry out a safety study of the experimental drug in patients at two centers. The study is set to begin in the coming weeks.

This remarkable story is not yet at its end, but a possible new treatment for patients with aPAP is now within sight. And the success does not stop there: The lessons learned about effective translational teams are now being applied across NCATS and promulgated to the research community. An African proverb says, “If you want to go far, go together”. Together, NCATS’ teams are going farther than ever before, making the translational process more efficient and effective, and thereby getting treatments to patients who so desperately need them.

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

Feb. 22, 2017: Catalyzing Progress on Rare Diseases across the Globe

“Translation is a team sport.” This is never more true than in research on rare diseases (defined as affecting fewer than 200,000 people in the U.S.) since people affected by, and researchers working on, any particular rare disease are by definition few and far between. The good news is that new scientific and communication platforms have made the formation and operation of widely dispersed research teams possible, and that sharing of information and expertise among these teams is starting to yield progress that was unimaginable only a decade ago.  

Two special events on either side of the Atlantic this month demonstrate the exciting progress being made in collaborative rare diseases research in the U.S. and across the world.

This Monday, February 27, NCATS and the NIH Clinical Center will host the 2017 celebration of Rare Disease Day at NIH. With the theme “Patients & Researchers — Partners for Life,” the event will include researchers, patients and their advocates, and policymakers, and will feature presentations, poster sessions, exhibits and even an art show. Please join us, and follow the event on social media using #RDDNIH. Rare Disease Day is an annual event observed around the world to raise awareness about rare diseases and their impact on patients’ lives, and research to improve the diagnosis, care and treatment of rare disease patients. At NIH, it serves as a day to bring together and highlight all the NIH Institutes and Centers that perform and support research on rare diseases.

Rare diseases are estimated to affect more than 350 million people worldwide, making understanding and treating rare diseases a global imperative. Earlier this month, I had the privilege of chairing a global conference of the International Rare Diseases Research Consortium (IRDiRC), which brings together funding agencies, patient groups, companies and scientists from around the world to share their insights and coordinate their work to accelerate progress in rare diseases. The underlying philosophy of IRDiRC is similar to that of NCATS: that more treatments will get to more patients more quickly via teamwork that improves the efficiency and effectiveness of the translational process. The IRDiRC global conference in Paris was enormously exciting, as participants both reported on remarkable new technologies that are greatly accelerating progress in rare disease diagnosis and therapy and demonstrated global eagerness to work together to make that progress a reality for all those living with rare diseases. IRDiRC is now in the process of finalizing ambitious new goals for the next decade, which I look forward to sharing with you when they are announced later this year.

Connect with NCATS often to learn more about our commitment to rare diseases research, including through our Genetic and Rare Diseases Information Center, the Rare Diseases Clinical Research Network, Therapeutics for Rare and Neglected Diseases initiative, the Clinical and Translational Science Awards Program, and more.

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

March 23, 2017: Achieving the Impossible Through Translational Teamwork

The workings of living things are replete with teamwork. Strands of DNA pair in complementary symmetry, proteins work with each other to turn on genes in exquisitely specific patterns, enzymes modify their molecular partners in a myriad of ways critical to life, and diverse cell types work together to function as an organ. Given nature’s example, it is perhaps curious that scientists frequently feel reluctant to work with others. Traditional scientific incentive and reward structures can reinforce this reticence. Translation absolutely requires teamwork for success, and many opportunities for translational success are missed because the right people, disciplines or organizations are not working together.

Via its unique science, organization and culture, NCATS is creating a collaborative ecosystem in which teamwork among diverse contributors is the norm. Two recent advances epitomize the enormous potential of this approach, each cracking a longstanding problem that had been previously intractable.

In the realm of clinical translation, patients and researchers often endure waits of months or even years for a clinical trial to begin, due to multiplicative ethics reviews by participating institutions’ Institutional Review Boards (IRBs). These delays are costly in financial and human terms: Patients may progress in their disease (making them ineligible for the trial) or even die while waiting for the trial to start. To overcome this roadblock, NCATS developed a platform for multisite trials for which all sites agree to rely on the review of a single IRB, greatly simplifying the process and time required.

What was once thought impossible — convincing institutions to sublimate their own processes to a united one — has now happened, thanks to the teamwork of literally hundreds of devoted physicians, ethicists and legal experts from around the country who worked to create the NCATS Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Reliance Platform. Today, NIH announced that all Clinical and Translational Science Awards (CTSA) Program sites have now signed the SMART IRB authorization agreement. This achievement makes single-IRB review possible for any clinical study that uses the NCATS CTSA Program network. CTSA Program awardees Harvard Catalyst, the University of Wisconsin-Madison Institute for Clinical and Translational Research, and Dartmouth SYNERGY led the team effort, which involved the close collaboration of all the CTSA Program sites as well as NCATS and other NIH staff. In total, more than 150 institutions have signed on to the agreement, with more to come. This collaboration promises to dramatically reduce waiting times for patients and translational researchers, with no loss of human subjects protections, and thus get new interventions to improve health tested for safety and effectiveness much more quickly.

On the pre-clinical front, scientists at NCATS and the University of Tokyo have come together to address another problem previously thought to be intractable, in this case finding a potential drug to treat parasitic roundworm infections that cause river blindness and lymphatic filariasis (elephantiasis) in more than 150 million people worldwide. A particular enzyme target offered an “Achilles’ heel” to kill these parasites, but previous approaches to finding a drug had repeatedly failed, leading to the conclusion that the target was “undruggable.”

The NCATS-Tokyo team developed a new approach to the problem that emerged from the diversity of the team members’ backgrounds: They created both a library of more than 1 trillion special peptides that they predicted would better fit the target’s unusual shape and a way to screen the peptides for activity against the critical enzyme. NIH will announce the team’s results when they are published in the coming weeks.

NCATS is following nature’s example, bringing together disparate minds and scientific disciplines and organizations to achieve what was previously impossible. This is, as we like to say, improving health through smarter science.

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

April 26, 2017: Sharing Translational Knowledge Is Smarter Science

While NCATS develops and disseminates many kinds of tools and technologies, the most powerful and most easily disseminated resource ever created is knowledge. Translational science, being a young field, does not have the accumulated scholarship and shared knowledge that characterize other fields of science. And since much translation was historically performed in biopharmaceutical companies where competitive product development, not publishing, was the primary aim, a culture of open publishing of translational successes and failures never developed. As academic organizations have engaged in more translation, they have frequently also adopted the practice of not sharing information due to competitive considerations.

As a result, the facts and causes of failure, so common in translation, are rarely shared, nor are the reasons for success. Any field of science that does not share its successes or failures will fail to progress. Therefore, predictably, translational science has only haltingly improved in understanding or effectiveness over the last several decades.

For these reasons, NCATS places great emphasis on knowledge dissemination and education and on creating a community of scholars — one that welcomes new investigators — who learn from each other and advance the field.

One of the principal tools in NCATS’ educational toolbox is the Assay Guidance Manual (AGM), a free online “how-to” guide to all the preclinical stages of translation. This remarkable resource provides both overview information and step-by-step protocols that, like valued recipes, include all the details needed to be truly enabling. The AGM now has 41 chapters, contributed by more than 100 scientists worldwide, and an international editorial board of experts from industry, academia and government. NCATS staff provide the AGM’s editorial and management oversight, including strategic direction for the frequent content updates and new chapters.

NCATS collaborates with the knowledge dissemination experts at NIH’s National Library of Medicine to host and manage the online content. In 2016, the AGM was accessed 375,000 times — more than 1,000 “hits” a day. These amazing analytics tell us there is a tremendous need and desire for good translational knowhow. NCATS staff also lead regular in-person AGM training workshops nationwide and are continuing to find new ways to share the information.

The AGM is a unique and groundbreaking resource for translational science. But equally important is the cultural shift its creation and flourishing represents: The AGM is the brainchild of visionary scientists at Eli Lilly and Company and what is now the NCATS Chemical Genomics Center who believed that sharing ways to produce robust, reproducible science would lead to the development of more interventions to improve human health. The vision of those founding Lilly and NIH scientists, so countercultural at the time, is now a major movement fueling translational science and, most importantly, getting more treatments to more patients more quickly.

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

May 24, 2017: NCATS Training Produces New Generation of Translational Research Stars

I am fond of saying that translation is a “team sport,” and like any team sport, translational science is inherently cross-disciplinary. Those training in this burgeoning field therefore must have not only robust education and mentoring in a scientific discipline on the translational team, but they must also have broad-based training in other disciplines. All that is in addition to a solid understanding of the scientific and operational principles of translational science. Through its Clinical and Translational Science Awards (CTSA) Program, NCATS is creating and implementing innovative training programs that are producing the translational science leaders of tomorrow. A few examples demonstrate why I am so excited about these young translational scientists.

Faheem Guirgis, M.D., is an emergency room physician at the University of Florida who is interested in understanding the causes and physiologic effects of sepsis — bloodstream infections — as a basis for better treatment. Using the skills and knowledge he acquired while working with experts in sepsis, oxidative stress and inflammation biology, along with classroom training in clinical and translational research design and methods, Guirgis made the leap from clinician to clinician-scientist by developing and launching a study for sepsis patients. He hopes to better understand the connection between sepsis and lipids in the blood and eventually identify new therapies.

Shawn Hingtgen, Ph.D., is a cell biologist and CTSA Program trainee at the North Carolina Translational and Clinical Sciences (NC TraCS) Institute. Through collaborations with an array of neurosurgeons, oncologists, stem cell experts, drug development specialists and others, Hingtgen created a potential stem cell therapy for glioblastoma multiforme, a deadly type of brain cancer. With guidance from NC TraCS investigators, Hingtgen has published stem cell therapy results of laboratory and mouse studies, established a start-up company based on the stem cell technology, and garnered NIH funding support for his research, all of which are paving the way to a new brain cancer therapy.

Lilyana Amezcua, M.D., is a University of Southern California assistant professor and neurologist who researches the genetic risk factors for multiple sclerosis (MS) in the Latino population of Los Angeles. She found that little was known about whether Latino social and cultural factors might also affect disease severity and progression, and her previous training had not given her the skills to find out. But thanks to the CTSA Program-supported community mentorship, Amezcua is now studying the perceptions and behaviors of Latinos with MS to determine those factors’ influences on the disease and enable the creation of interventions to address them.

I firmly believe that all academic translational science training should include an externship in a non-academic component of the translational ecosystem, such as a biotechnology or pharmaceutical company, a regulatory agency, or a patient group. I am therefore delighted that the first partnership to provide externships to CTSA Program grantees has gotten underway. NCATS has partnered with Eli Lilly and Company to offer externships for CTSA Program scholars, trainees and investigators. Participants receive training in product development-oriented clinical trial design, clinical pharmacology, toxicology, regulatory affairs and other critical drug development processes. The first group of Lilly externs found the experience invaluable to their career development, and we are now expanding the program. I look forward to telling you more about this exciting new direction for translational training. Connect with NCATS to make sure you hear the latest!

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

June 21, 2017: NCATS-FDA Community Engagement Helping Advance Translational Success

“Begin with the end in mind.” This business leadership mantra also is critically important in translation, but defining “the end” correctly can be difficult due to the complexity and diversity of the translational process, in which success is viewed differently from one stage to another. Well-meaning scientists often produce quality work that is highly regarded at their respective translational stage but is not acceptable for or even relevant to the next. This leads to wasted effort, mutual exasperation and — most importantly — failure to reach patients in need. 

This core characteristic of translation — which literally means “to carry across” — explains why NCATS is so focused on what we broadly call “community engagement,” with “community” defined differently depending on the stage of the translational process. Translational scientists must assume that what constitutes success to them is not what represents success to those to whom they are “carrying across.” Once this critical assumption is made, it is obvious that the only way to find out what will be successful across all stages is through community engagement. 

NCATS’ engagement with the regulatory community, specifically the Food and Drug Administration (FDA), is particularly important. Not every intervention that can improve human health is regulated by the FDA, but many — including drugs, devices and diagnostics — are. Traditionally, academic scientists have not been taught about the FDA or regulatory requirements, since publishing papers on scientific advances has been necessary and sufficient for their career success. But as more and more academic scientists become interested in translating discoveries to human health improvements, they often assume that the information needed for a publication is the same as that needed by the FDA to approve a new drug or device. That incorrect assumption is a very common cause of good science failing to progress in translation. 

To address this common translational roadblock, NCATS engages with the FDA on programs encompassing training, tool development and joint research initiatives. For example, NCATS and the FDA work together in our Tissue Chip for Drug Screening, Toxicology in the 21st Century, and Collaborative Use Repurposing Engine (CURE) programs. FDA input has been crucial to these programs’ success and impact. 

NCATS also partnered with the FDA as well as other international regulators and research organizations to create the Global Ingredient Archival System (ginas), which enables substances to be defined by a standardized, common identifier. The ginas software makes it more efficient for the FDA to review new drugs and identify safety concerns. The FDA, the European Medicines Agency and other agencies have adopted the system, which will facilitate communication with the worldwide health community. 

In addition, NCATS played a lead role in the NIH-FDA Joint Leadership Council’s development of the recently launched NIH-FDA clinical trial protocol template tool. This tool’s standardized format will make the writing and review of protocols easier and faster and will ensure that clinical protocols have all the information the FDA needs to evaluate studies of investigational new drugs and devices. NCATS also helped lead efforts for the Council’s Biomarkers, EndpointS, and other Tools (BEST) Resource, which provides a common language for NIH, the FDA and other researchers to use when communicating about biomarkers. 

Beginning with the FDA end in mind, NCATS is improving health through smarter science.

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

July 25, 2017: Engaging Patient Communities to Advance Translational Science

NCATS’ scientific goals include discovering new insights and approaches that will make the translational process more effective and efficient. One such potential breakthrough approach — involvement of patient communities in the translational science process from the outset — has shown striking success in individual cases, such as in the development of interventions for the rare disease cystic fibrosis. But as in so many areas of translation, there is no general understanding yet of what practices in patient community engagement lead to improved translational success. So, true to our mission, NCATS is taking a systematic approach to this question, aiming to develop a translational science of patient community engagement, which can be applied to any translational research project to make it more effective.

Our Center took a big step forward in this effort on June 30, 2017, at NCATS Day: Partnering with Patients for Smarter Science. Attended by dozens of patients, caregivers, support organization representatives and social scientists — and nearly as many NCATS scientists and staff — the day was structured as a two-way dialogue. Attendees engaged directly with NCATS staff to learn from each other: attendees about Center programs and initiatives with which they might engage, and NCATS staff about how attendees thought NCATS could most effectively involve patients at every stage of the translational science spectrum.

The day began with a striking case study: the Center’s collaboration with the Alpha-1 Foundation to find treatments for alpha-1 antitrypsin deficiency, a rare disease characterized by liver and lung damage. Though the purpose and progress of the project were presented, more important to the day was the joint discussion of success factors — that is, what explained the remarkably successful pace and productivity of the collaboration — and how they could be applied to other projects. Insights included details on team composition, project plans, milestones, focus and continuous communication. 

Next, NCATS scientists from each of the Center’s programs presented a brief description of how their program currently works to incorporate patient engagement. In the breakout groups that followed, attendees provided feedback on current efforts, suggestions for improvements and entirely new areas of opportunity and need. In a rich final session, conclusions were summarized and an action plan for next steps created, which NCATS is now using to improve its programs and to plan for continuation of this enormously valuable and important interchange.

The next big event in our patient community engagement efforts will be on Sept. 8, 2017, when we will host the patient community for the NCATS Toolkit for Patient-Focused Therapy Development: Demonstration and Dissemination Meeting. This event will unveil, explain and plan future development of the Toolkit, an online portal developed in collaboration with patients and rare disease advocates as a gateway to “how-to” resources and tools that span the therapy development landscape, including how to:

  • Establish a patient registry;
  • Drive patient-focused discovery and pre-clinical research and development;
  • Work with NIH and the Food and Drug Administration; and
  • Conduct post-market surveillance.

Register now to attend!

Through these efforts, NCATS is developing the translational science of patient community engagement — a key part of our mission to improve health through smarter science.

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

Aug. 22, 2017: Overcoming Challenges to Move Stem Cell Therapies to the Clinic

The promise and perplexity of stem cells have captivated me for decades. During my medical training, I took care of patients with neurological diseases caused by death of brain cells — such as Alzheimer’s, Parkinson’s and stroke — diseases we imagined could someday be treated by new neurons made from stem cells. During my research training, I sought to understand the basic biology of stem cells in the brain, what signals instruct them to become one type of cell or another during normal development, and what happens when that process goes wrong. The idea that stem cells, which are capable of becoming any cell in the human body, could be produced at will in the lab from adults — including the patients in my clinic — seemed to be a far-fetched pipe dream. Like so many other remarkable advances in science over the last three decades, that pipedream is now a reality. Induced pluripotent stem cells (iPSCs) are now being produced routinely, usually from adult skin cells. Particularly when combined with new gene-editing technologies, the promise has never been greater for stem cell-based therapies to help treat millions of patients with spinal cord injuries, diabetes, Alzheimer’s disease and scores of other disorders.

Despite this amazing progress, we have yet to achieve the hoped-for promise of stem cell therapies in treating disease. The barriers are typical of those encountered in all areas of translational science. We need to understand how to create, characterize and differentiate patient-specific iPSCs in well-defined, reproducible and efficient ways that meet regulatory standards, and systematically understand the beneficial and potential adverse effects of these cells in people.

To address these challenges, the NIH Common Fund Regenerative Medicine Program helped NCATS create the Stem Cell Translation Laboratory (SCTL), which officially opened last month. The planning, design and construction of this purpose-built, state-of-the-art laboratory took more than two years and marks a new and exciting phase for stem cell translational science. NCATS will use the its signature, systems-driven collaborative approach to characterizing stem cells and their differentiated progeny, creating efficient and scalable differentiation protocols, and disseminating all its protocols and data for use by the scientific community. Among other technologies, the SCTL will integrate multiple “‑omics” technologies (e.g., genomics and proteomics) with single-cell analysis and functional cell characterization. The SCTL is now seeking collaborators from academic, biopharmaceutical and nonprofit organizations to partner in technology development, demonstration and dissemination projects.   

SCTL is just one NCATS initiative to advance stem cell translation to the clinic. Investigators at Boston University and three other CTSA hubs funded through NCATS’ Clinical and Translational Science Awards (CTSA) Program established a national network of iPSC repositories and core facilities. The iPSC network was funded through NCATS’ first round of CTSA Program Collaborative Innovation Awards and already includes more than 1,000 patient-derived iPSCs with plans to add thousands more. Leading the effort to openly share advances in the stem cell field, the repository also contains gene-editing tools and protocols for CTSA Program investigators to enhance basic and clinical research, including better disease modeling and development of regenerative medicine therapies.

On Sept. 26, 2017, NCATS will host a workshop on translational challenges related to iPSCs. This meeting will convene diverse scientists on the NIH campus to discuss barriers to progress and work toward concrete solutions. Register now to attend!

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

Sept. 25, 2017: Putting Patients in the Driver's Seat in Rare Diseases Research

An abiding anomaly in translation is that the people intended to benefit from an intervention are generally excluded from its creation. Drugs and other interventions intended to improve human health are consumer goods, and organizations that make other such goods (think toothpaste and clothing) involve potential consumers in every part of the creation of a new product. And when consumers identify needs that current products do not meet, they routinely start new companies to do so. 

These things have rarely happened in translation, with the unsurprising result that many medical needs remain unmet, particularly for rare diseases, and interventions that are developed may not meet the most important needs of patients. I believe that changing this historical practice is one of the translational science innovations with the greatest potential to get more treatments to more patients more quickly. In fact, one of my first directives to the NCATS staff on becoming director almost five years ago was to involve patients in every project we do from the beginning, and to develop the science of patient and community engagement, with best practices that can be disseminated to all doing translational research. 

Earlier this month, NCATS took its biggest step yet in achieving this vision with the release of the Toolkit for Patient-Focused Therapy Development on September 8 at a public meeting on the NIH campus. The Toolkit is a centralized portal of the “how-to” resources and tools that patient support organizations can use to advance translation for their diseases, from discovery though clinical trials, to regulatory and industry interactions, to post-approval access issues. And though the resources are focused on rare diseases, the approaches and tools are applicable to all diseases, both rare and common. Fittingly, the Toolkit was developed via a close collaboration between the rare diseases patient advocacy community and the NCATS Office of Rare Diseases Research. Please have a look, tell us what you think, and give us suggestions for improvements or tools not represented that we should add.

In related news, I am delighted to update you about the International Rare Diseases Research Consortium (IRDiRC), which I currently chair. IRDiRC brings together funding agencies, patient groups, companies, and scientists to coordinate and thereby accelerate progress in rare diseases research worldwide. Last month, new IRDiRC goals (PDF - 294KB) for the next decade were announced in a Nature commentary, and accompanying past reflections and future perspectives were published in Clinical and Translational Science. The goals include the accurate diagnosis of all patients with a rare disease within a year of their first consulting a physician, developing 1,000 new therapies for rare diseases, and creating methods to evaluate the impact of these efforts on rare disease patients. These goals are extremely ambitious but IRDiRC believes they are achievable via new globally collaborative team-approaches and the singular convergence of scientific opportunity and medical need in rare diseases.

Both NCATS and IRDiRC believe that translation is a “team sport”, and that with patients on the team, progress at every step of the translational science process will be more efficient, effective and relevant to the health of people living with diseases.  

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

Oct. 23, 2017: Forging Strong Collaborative Links Among CTSA Program Hubs

Answering today’s complex scientific questions requires considerable resources, including deep expertise in multiple disciplines; a wide variety of analytical and computational tools; and access to well-curated, harmonized data. NCATS’ Clinical and Translational Science Awards (CTSA) Program supports more than 50 academic medical institutions — called hubs — each of which is its own translational science powerhouse that is fundamentally collaborative in structure.

NCATS strives to find new ways to help leverage the hubs’ individual strengths through opportunities to collaborate at the regional and national levels, such as through the new CTSA Program Data to Health (CD2H) project. Designed to support the CTSA Program consortium and eventually a broader biomedical research informatics community with open data and software as well as other resources, awardees began work to establish a CD2H coordinating center last month.

Another way that NCATS stimulates the hubs’ research is through the CTSA Program Collaborative Innovation Awards (CCIAs). This support helps foster collaboration among three or more hubs to work together to develop, demonstrate and disseminate innovative experimental approaches to overcoming systemwide translational science roadblocks.

In 2016, NCATS issued the first seven CCIAs to 24 collaborating hubs. Three of these hubs — the University of Alabama at Birmingham, Vanderbilt University and the University of Massachusetts Medical School — are working together on a research project called Strengthening Translational Research in Diverse Enrollment (STRIDE). STRIDE is designed to create an integrated, multilevel, culturally sensitive intervention to engage African Americans and Latinos in translational research.

Another CCIA project involves Boston Children’s Hospital (Harvard University); the University of California, Los Angeles; and the University of Cincinnati in setting up the Disseminating Curative Biological Therapies for Rare Pediatric Diseases Consortium. The goal is to more rapidly translate complex gene and cell therapies to early phase pediatric clinical trials. A network of pediatric centers with unique expertise in complex gene therapies will support investigators across multiple CTSA Program hubs with development of pre-clinical studies, product manufacturing, unique laboratory assays, and regulatory management for clinical trials to assess safety and effectiveness.

In addition to innovating to solve longstanding translational roadblocks, a major strength of the CTSA Program is that it helps foster connections among experts nationwide in wide-ranging fields to respond to emergent health issues. Later this month, I’ll be asking CTSA Program hub investigators to brainstorm with me and other scientists from NCATS and the NIH National Institute on Drug Abuse about research needed to develop solutions for one of the greatest crises facing our nation today: the opioid epidemic. A particular challenge of the opioid crisis is that it requires solutions across the translational spectrum, from therapeutic development to new clinical trial strategies to novel recruitment and adherence approaches. The strength and diversity of the CTSA Program hubs constitute a unique national resource that addresses this entire spectrum — a resource that is ideally suited to the effort to get more treatments for the opioid epidemic to more patients more quickly. 

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

Dec. 1, 2017: Accelerating Gene Therapy

I have previously written of NCATS’ work to accelerate the development of various types of therapeutics. From small molecules to proteins to stem cells, each modality works in a different way to reverse a disease process. I want to bring you up to date on some of the work NCATS is doing using DNA or RNA genes to treat diseases, aka “gene therapy”. 

In August 2017, the Food and Drug Administration (FDA) approved its first U.S. gene therapy product: a treatment for cancer in which a therapeutic gene is delivered to a patient’s blood cells outside the body and the cells are then delivered to the patient. This process is sometimes termed “ex vivo” gene therapy. Two months later, in October, an expert advisory panel to the FDA unanimously endorsed a gene therapy delivered directly to the patient, (“in vivo” gene therapy), in this case, to the retina of the eye to treat a rare form of hereditary blindness.

These important milestones are the most recent signs of the renaissance of gene therapy, a modality for which the translational chasm between promising concept and realized patient benefit has been unusually wide. But now the translational science of gene therapy has progressed to the point of clinical successes. 

NCATS is at the forefront of addressing translational challenges that have hindered progress in this field. For example, in my October 2017 Director’s Message, I wrote about a collaborative project within our Clinical and Translational Science Awards (CTSA) Program to more rapidly translate complex gene and cell therapies to early phase pediatric clinical trials. And, through our Therapeutics for Rare and Neglected Diseases (TRND) program last year, NCATS initiated a suite of gene therapy collaborations to develop solutions for bottlenecks limiting efficient gene therapy translation.

One of these TRND projects is a gene therapy for the rare pediatric disease aromatic L-amino acid decarboxylase (AADC) deficiency. Our project partner, Agilis Biotherapeutics, Inc., achieved a regulatory milestone when the FDA gave them the green light to file an application for approval to market the gene therapy to patients. Just one year earlier, the therapy had seemed destined to fail: Despite promising results in clinical trials outside of the U.S., the market for this disease is small and the work needed to proceed was seemingly insurmountable. NCATS teamed with Agilis to convert promise into reality, jointly creating a manufacturing process for the therapy that complies with FDA regulations and obtaining pre-clinical data required by the FDA. In addition to getting this potentially lifesaving therapy to patients, this project established technological and regulatory models that will accelerate the development of other rare disease gene therapies.

NCATS is now exploring ways to streamline the development of gene therapies generally. These treatments rely on delivery of the gene to a specific cell type, usually by a modified virus called a “vector.” I like to think of the vector as a suitcase carrying the gene, and currently, the FDA must evaluate both the suitcase and the gene inside with every new product.

One idea we are pursuing is the development of standard vectors — like standard-sized suitcases we use for travel — that could be used for multiple diseases that affect the same cell type. In this scenario, the manufacturing processes, safety and location of vector delivery of the gene would be known, so the FDA would only have to review the relevant gene being carried, reducing time to approval and making the process more cost-effective. NCATS requested information on this approach from the scientific, regulatory, industry and patient communities this fall, and we now have received feedback that will help us identify opportunities, challenges and translational science needs for platform vector gene therapy.

These efforts that involve multiple NCATS programs, institutions and public-private partnerships exemplify our guiding principles that “translation is a team sport,” and that therefore, “if you want to go far, go together.” Together, we are going far in gene therapy.

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