Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed)

The purpose of this funding opportunity announcement (FOA) is to solicit applications for pilot projects to elucidate a role for understudied proteins associated with rare diseases. Awards will support generation of preliminary data and/or tools around eligible understudied protein(s).Funding Opportunity Description Introduction The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH), is transforming the translational science process so that new treatments and cures for disease can be delivered to patients faster. NCATS strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients. This funding opportunity announcement (FOA) aims to promote innovative research to increase knowledge of understudied proteins associated with rare diseases. The submission of small research grant (R03) applications is encouraged from institutions and organizations proposing projects leading to a better understanding of eligible proteins listed below. Small research (R03) grants provide flexibility for initiating discrete, well-defined projects that realistically can be completed in one year and require only limited levels of funding. This program supports different types of projects including, but not limited to, the following: Pilot or feasibility studies; Small, self-contained research projects; Development of research methodology; and/or Development of assays to support compound screening projects; Development of human cell or animal based models. These awards will support generation of preliminary data and tools around eligible understudied protein(s) with the intent of elucidating the function of these proteins in the context of rare disease and obtaining sufficient preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. These grants are non-renewable. This Funding Opportunity Announcement does not accept applications proposing clinical trial(s). Background The human genome has revealed a great deal about the human proteome, though significant portions of the genome remain understudied. Only a subset of expressed proteins demonstrates the requisite properties to serve as targets for the development of therapeutics. Many bona fide drug targets likely remain to be studied in the Druggable Proteome (DP), which can be defined as the fraction of proteins which have the ability to bind drug-like molecules. The term "drug-like" refers to the physical, biochemical, and pharmacological attributes of small molecule compounds that are generally recognized to be required for efficacious clinical drugs in humans. While the number of proteins in the DP is upwards of 4,500, the existing clinical pharmacopeia is represented by only a few hundred targets, leaving a huge swath of druggable biology unexploited. The expanded exploration of the relationship between the protein and the rare disease phenotype, or the development of a useful tool or reagent can accelerate research into a previously understudied protein. Many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial catalyzing event (e.g., association with a biologic process or phenotype, creation of tools or reagents for the protein, etc.) has not yet occurred. The purpose of this FOA is to spark such catalyzing events through the support of small R03 awards to identify novel drug targets for the treatment of human disease, specifically rare disease Objectives and Scope The goal of this specific solicitation is to provide a needed opportunity for the collection of preliminary data around the role of understudied proteins associated with rare diseases. This FOA will provide funding to support research that will characterize new targets for treatment of human disease among the understudied proteins of the Druggable Proteome. These projects should be carried out in a short period of time with limited resources as defined by the funding mechanism. It has been recognized through workshops and publications that understudied proteins become illuminated when (1) there are tools to study the protein (e.g., tools that modulate protein activity) and/or (2) there is biochemical, cellular, or animal model evidence of disease/physiological relevance. This FOA was developed to address the need for expanded research and validation experiments on eligible understudied protein(s), with the intent of producing preliminary data to address the lack of biochemical, cellular, or animal model data associated with many understudied proteins. It is expected that the award will be used to obtain preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. The NIH supports research on a broad range of diseases that are defined as rare; that is diseases affecting fewer than 200,000 individuals in the United States (per the Rare Disease Act of 2002). Collectively, there are an estimated 7,000 rare diseases, which affect approximately 25-30 million people in the United States. Most are serious or life-threatening, with a disproportionate number of rare diseases affecting children. At this time, effective treatments are available for fewer than 5%. The IDG Program has linked over 6,000 proteins to rare diseases, with over 80% of these proteins considered extremely understudied. For the purposes of this FOA, eligible proteins are those that have an association with rare disease through data mining of the encyclopedia of rare disease annotations for precision medicine (eRAM) and Orphanet, are considered understudied (those proteins that lack small molecule binders and/or have limited biological characterization) and are within a protein family that is traditionally considered druggable.