P50AR080581

Achilles Tendinopathy Center of Research Translation - Abstract

The Achilles Tendinopathy Center of Research Translation (AT-CORT) at the University of Pennsylvania will foster fundamental discoveries to guide clinical translation, as well as develop and employ novel translational resources, models, and technologies to address the highly significant research and clinical challenge of Achilles tendinopathy.

Despite the high frequency and increasing prevalence of tendinopathy in young and old patients, and the significant pain and disability that arises from this condition, as well as the associated high cost to society, effective treatment modalities have stagnated over the last two decades. This is due to the lack of fundamental understanding of tendon disease etiology and pathogenesis, which limits the development of novel treatment modalities.

At present, beyond surgical intervention for late-stage disease, the only approved clinical therapy involves physical interventions via controlled rehabilitation mechanical loading of the tendon. While efficacious in some patients, outcomes of this intervention do not stem disease progression in most patients. Given the central mechanical role of the Achilles tendon and the critical role of mechanical loading and mechanobiology on tendon cell homeostasis, it is critical that we develop and expand our understanding of the role of mechanical forces in disease onset and progression to optimize existing and inform new treatment strategies.

Our proposed AT-CORT is uniquely positioned with a critical mass of multidisciplinary scientists and clinicians with strong interest and expertise in these and related areas. The overall goal of the AT-CORT is to develop new insight and technologies that uncover the mechanobiologic basis of Achilles tendinopathy across length scales, from the nucleus, to the cell, to the tissue microenvironment to patients. We will assess these critical elements during disease onset and progression, informed by both in vivo animal models that replicate disease processes and source material and real-world loading data from living human subjects.

The AT-CORT is comprised of four independent and yet interactive elements, including an administrative core to oversee and guide interactions and primary research projects focused on the transfer of information from the external tendon cell microenvironment through the cytoskeleton (Project 1) and on chromatin remodeling and mechano-epigenetic regulation of tendon cell phenotype (Project 2). Using cells, tissue, and loading information derived from both human and animal tendinopathic models (Tissue Core), these research projects will advance our knowledge of the origins of tendinopathic disease and define new avenues for therapeutic intervention.

Together, our highly interdisciplinary team, innovative tools, and outstanding and interactive research projects and cores will dramatically advance knowledge, develop innovative tools and insight, and provide new directions for translation of novel therapies to treat Achilles tendinopathy.

Trustees Of The University Of Pennsylvania

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.846 - Arthritis, Musculoskeletal and Skin Diseases Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

Pennsylvania United States

State-Wide

NIAMS Centers of Research Translation (CORT) (P50 - Clinical Trial Not Allowed) (RFA-AR-22-001)

Amendment Since initial award the total obligations have increased 210% from $1,561,239 to $4,842,665.