Retreat Topics iPSC Opportunities in NIAMS Diseases Science Management Forum: Leveraging and Strategic Funding Collaborations Atopic Dermatitis Advancing Research on Tendon and Ligament Biology Clinical Trials Portfolio Analysis and NIAMS Goals for Clinical Research

iPSC Opportunities in NIAMS Diseases: Topics What NIAMS diseases/conditions and research areas are poised to take advantage of recent advances in iPSC technologies, and would adoption of iPSC approaches accelerate progress? What are the current limitations in the use of iPSCs for these applications? Are there appropriate in vitro cellular models for common and rare diseases of interest to NIAMS that could be generated from patient-specific iPSCs?

iPSC Opportunities in NIAMS Diseases: Topics, cont. Are any of these models ready for 1) studies of disease pathogenesis, 2) functional studies of gene variants, 3) high-throughput drug screening, 4) drug toxicity studies, and 5) studies of gene repair? What are the technological hurdles, and are special resources required to overcome them? What are the opportunities for leveraging and partnerships?

iPSC Opportunities: Discussion Best Practices/Goals: Challenges Streamline communication and enhance collaboration throughout the community Efficient and reliable cell reprogramming and differentiation techniques and protocols Standardize terminology and protocols Cell sorting and purification Establish common regulatory and tech transfer protocols Safe and efficient genetic “correction” methods Opportunities Complex diseases Immune response Monogenic diseases Therapeutic delivery methods Disease-specific and /or personalized tissue models Centralized resources (repository, cell manufacturing facilities, iPSC control lines)

Leveraging and Strategic Funding Collaborations: Topics What partnerships—within NIH and externally—can leverage the NIAMS research investment? Collaborative funding: benefits and challenges Pilot project/seed funding Sustaining registries Infrastructure for planning groups Industry expertise and resources in therapeutic and biomarker research

Leveraging and Strategic Funding Collaborations: Discussion Collaborative funding strategies with NIH Public-private partnerships Involvement of funding partners and patient advocacy groups Cooperation of multiple Institutes and Centers to understand complex diseases/comorbidities The Osteoarthritis Initiative example Co-development of initiatives Buy-in from industry leaders Common Fund Unique resources provided by industry partners Leveraging funding from non-federal not-for-profit organizations Important leadership role for NIH “Proving ground” for innovative concepts Bridge funding for new investigators seeking NIH support

Atopic Dermatitis: Topics What are the opportunities for accelerating research in atopic dermatitis (AD) that can lead to new therapeutic targets? What are the main factors that contribute to severe AD? What translational research opportunities have emerged from recent studies on the biology of AD? What are the opportunities, needs, and barriers to proof-of-concept trials in AD? What challenges arise with conducting trials in specific patient populations (e.g., children, variation in disease severity), and how can they be overcome? How should comorbidities be addressed, and what insights do they provide?

Atopic Dermatitis: Discussion Mechanisms of disease/disease susceptibility Future research directions Identification of primary disease etiology: barrier defect or immune dysfunction? Barrier disruption Better characterization of barrier defects and immune system effects on barrier function Immune dysfunction Clinical presentation and clinical research Comorbidities Emerging opportunities for intervention Phenotyping complications Challenges with pediatric trials Molecular messengers (cytokines) in immune function Treatment modalities: systemic vs. topical Regulators of epidermal barrier and cell-cell junctions Quality of life outcomes

Advancing Research on Tendon and Ligament Biology: Topics What are the opportunities for exploring the basic biology of tendons and ligaments? How can knowledge of tendon and ligament developmental biology inform tissue engineering and regenerative medicine approaches? Are failures and limitations of the current “bedside” approaches to tendon and ligament injuries pointing to gaps in our understanding of the basic biology of these structures? What are the most immediate clinical needs, and how can these gaps be addressed by investment in basic science?

Advancing Research on Tendon and Ligament Biology: Topics, cont. What are the obstacles in exploring the basic biology of tendons and ligaments? Does this area have a sufficient workforce/pipeline in basic research relevant to tendons and ligaments?

Tendon and Ligament Biology: Discussion Basic research opportunities Clinical needs Repair and rehabilitation strategies Tendon and ligament structure and mechanical properties Engineered grafts don’t behave like normal tendons and ligaments Pre-injury degeneration Tendon development and healing Strategies to repair large tears of the rotator cuff Obstacles Role and appropriate use of growth factors Better animal models Small research community Role of inflammation (+/-) Platelet-rich plasma Stem cells

Clinical Trials Portfolio Analysis and NIAMS Goals for Clinical Research: Topics How do we define the impact of completed studies? What are the most meaningful measures of success or predictive performance indicators? Are there over- or under-represented areas in the NIAMS portfolio? What approaches could be used to determine whether NIAMS is supporting the most important studies and how to achieve that goal? What is NIAMS’ role in promulgating results of significant clinical trials and studies?

Clinical Trials: Discussion Impact Questions to consider before accepting a clinical trial application Beyond influencing clinical practice and public health policy – the most important goals – trials may inform future research particularly if they contain some mechanistic studies. If this trial is successfully completed, will findings guide the field? Will they tell us about more than just the disease being studied? Dissemination How timely is this trial – will events make it meaningless? Requirement to provide results to clinicaltrials.gov may not be sufficient Do investigators have evidence (e.g., from electronic medical records) that they can recruit enough patients for a meaningful study?