CAN Review Board Concept Clearances

Concepts describe the basic purpose, scope and objectives of proposed initiatives and represent an early planning stage for potential NCATS activities.

Concept Clearances

Contact

Anna L. Ramsey-Ewing, Ph.D.

Gregory P. Jarosik, Ph.D.

Concepts are discussed with the NCATS Advisory Council and Cures Acceleration Network (CAN) Review Board and through other public venues. Council approval of a concept does not guarantee it will become an initiative. That decision is made based on scientific and programmatic priorities and the availability of funds.

View approved CAN Review Board concept clearances by year:

2020

Biomedical Translator—User Interface (UI) Development

Jan. 16

Christine M. Colvis, Ph.D., presented a contract concept for developing a UI for the NCATS Biomedical Translator (Translator). Approved in December 2015, the Translator program aims to enable exploring computationally assisted knowledge graphs and constructing new research hypotheses. NCATS has completed the feasibility phase of Translator and moved to the development phase. Dr. Colvis explained that NCATS has invested in user-centered design work for the UI, but not its development.

The goals of this concept are to develop an agile UI for Translator that will allow the broader research community to use Translator and provide researchers the ability to query the data system for key information for addressing research questions. NCATS recognizes that proper execution of user-interface design will require collaboration involving a team with expertise in user-centered design and biomedical science. In 2019, NCATS engaged the 18F (an abbreviation for 1800 F Street) Office, Technical Transformation Services, General Services Administration, to conduct user-centered design research and identify core use cases. The 18F report recommended engaging interface developers through a contract mechanism.

Aside from delivery of a Translator UI that is intuitive for researchers, other expected outcomes will be an unprecedented view of biomedical information and data presentations that enhance human reasoning and understanding of specific aspects of medicine, both biologic and physiologic. No broadly used system like Translator currently exists elsewhere. All results and software developed will be publicly available through GitHub. For the long term, Translator aims to foster community-driven adoption of data-sharing standards and practices.

Project/Program Officer:
Christine M. Colvis, Ph.D.
Director, Drug Development Partnership Programs
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-451-3903
Email: ccolvis@mail.nih.gov

2019

Microphysiological Systems Scientific Conference: International Standardization and Harmonization of Microphysiological Systems

Dec. 13

Dr. Tagle presented a concept for sponsoring an MPS scientific conference to promote international standardization and harmonization of MPS. Several recent activities warrant development of an international standard. In fact, the MPS technology has expanded internationally, and progress has been significant in developing MPS for a number of human organs and organ systems. Tissue chips and other 3-D models are converging in application.

The goals are to lay the groundwork for an orderly transition of MPS strategic, organizational and funding aspects to other stakeholders; convene annual scientific conferences; use these forums as the main conduit of information, technology and data sharing; and establish a training environment for the next generation of MPS scientists.

NCATS anticipates that the outcome—an international scientific conference devoted to MPS—will be self-sustaining through registration fees and sponsorship after a brief period of CAN support. One major effect will be an increased awareness in the research community about the potential use of tissue chips in drug development as an approach that more accurately reflects the human response when compared to existing in vitro and in vivo animal models.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Associate Director for Special Initiatives
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: tagled@mail.nih.gov

Microphysiological Systems (MPS) Database Center

Sept. 19

Danilo A. Tagle, Ph.D., presented the concept re-issue to continue the Microphysiological Systems (MPS) Database Center (DC) currently hosted and managed by the University of Pittsburgh Drug Discovery Institute. Dr. Tagle noted that establishing the MPS Database Center was first approved on Sept. 7, 2017, by the Council and Board as database support for the Tissue Chip Program. The MPS Database—which is the central archive for aggregate preclinical, clinical and experimental MPS data generated in the Tissue Chips Testing Centers (TCTCs)—also is being used by developers and other stakeholders, including the pharmaceutical industry. To date, the database contains 58 MPS (i.e., tissue chips) experimental models covering 11 organ systems, which were developed at 14 TCTCs. Data from 171 studies are being housed, including images and videos deposited by eight data developers. Dr. Tagle emphasized that all data submitted to the MPS DC will be made publicly available to the research community.

Since November 2018, the MPS database usage has steadily increased: 109 users are currently registered and, on average, 86 new users view or download data each month. The MPS database has the potential to transition to a self-sustaining business model after the 2-year funding cycle. Dr. Tagle summarized the ongoing research activities in this area and noted that the MPS Database Center is a collaborative partnership between NCATS, the FDA and the MPS affiliate of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ).

Order of Magnitude Increases in the Efficiency of Adeno-Associated Virus (AAV) Vector Production for Human Gene Therapy

May 16

Multiple clinical successes in clinical trials using Adeno-Associated Virus (AAV) vectors have been witnessed in recent years. At present, the major limiting factor to extending this approach to other rare diseases is the ability to manufacture clinical-grade AAV vectors.

The objective of this initiative is to develop at least one independently validated technology that increases efficiency of AAV vector production for human gene therapy by a factor of tenfold or more. If successful, this initiative would substantially increase the number of rare disease gene therapy clinical trials. In addition, the developed technology could be used for research projects conducted by NCATS’ Division of Preclinical Innovation.

Project/Program Officer:
Philip John (P.J.) Brooks, Ph.D.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-443-0513
Email: pj.brooks@nih.gov

Synthetic Technologies for Advancement of Research and Therapeutics (START) – Engineering Novel Therapeutics

Jan. 10

The objective of this initiative is to employ synthetic biology (SB) – along with newly available tools in genetic engineering, gene synthesis and metabolomics – to construct and incorporate new biosynthetic or artificial metabolic pathways to accelerate and enable the design and construction of engineered cell therapies for the production of compounds with a strong therapeutic and disease relevance. SB can be applied in a variety of ways for therapeutic development for a number of diseases, such as for metabolic diseases through the construction and clinical implementation of mammalian synthetic gene networks that can accurately detect dysregulated metabolic signals and initiate the production and delivery of appropriate dosage of therapeutic molecules/compounds.

The program will focus on developing desired synthetic therapeutic products in a scalable, cGMP compliant manner; generating a catalog of biologically relevant pathways that can be used in a “plug-and-play” scenario to generate biologics; engineering novel protein motifs that increase bioavailability in currently difficult to target tissue types; and expanding the available catalog of biologics used to treat diseases, such as rare metabolic disorders.