BLRD Research Career Scientist Award Application.

BLRD 研究职业科学家奖申请。

• 批准号: 10366566
• 负责人: Hee-Jeong Im Sampen
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366566
• 关键词: Achievement; Address; Adverse drug effect; Adverse effects; Affect; Afferent Neurons; Age; Animal Model; Animals; Antibodies; Antibody Therapy; Antineoplastic Agents; Area; Arthralgia; Arthritis; Automobile Driving; Award; Behavioral; Cartilage; Cells; Chronic; Clinical; Clinical Trials; Complex; Data; Degenerative polyarthritis; Disease; Disease Progression; Drug Formulations; Economic Burden; FDA approved; Genes; Goals; Hyaluronic Acid; Individual; Injections; Injury; Joints; KDR gene; Knee Osteoarthritis; Knee joint; Life; Ligands; Low Back Pain; Medical; Medical Assistance; Military Personnel; Modeling; Molecular; Morbidity - disease rate; Mus; Musculoskeletal Pain; Nerve Growth Factors; Nociception; Operative Surgical Procedures; Opiate Addiction; Opioid; Pain; Pain Origin; Pain-Free; Pathology; Pathway interactions; Patients; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase III Clinical Trials; Prosthesis; Publications; Quality of life; Replacement Arthroplasty; Reporting; Research; Rhubarb food; Role; Scientist; Severities; Source; Spinal Ganglia; Symptoms; Synovial Membrane; Technology; Testing; Therapeutic; Time; Tissues; Transgenic Mice; Treatment Cost; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Veterans; Work; addiction; base; bevacizumab; blood vessel development; bone; career; cartilage degradation; cartilage regeneration; chronic pain; cost; disability; drug efficacy; effective therapy; factor J; glial activation; health management; inflammatory pain; innovation; insurance claims; novel strategies; osteoarthritis pain; pain reduction; pain relief; pain sensation; pain symptom; personalized medicine; pre-clinical; prevent; receptor; small molecule; social; tissue regeneration; transmission process; treatment risk; treatment strategy

ABSTRACT: Osteoarthritis (OA), commonly referred as arthritis, causing painful joints, is among the most common chronic conditions among veterans. Indeed, the condition is much worse among veterans than non-veterans; one of every four veterans lives with a serious arthritic condition and individuals over age 40 are twice as likely to develop arthritis after returning to civilian life. Osteoarthritic symptom, pain, is the key reason to seek medical assistance, yet there is no effective way to relieve OA-induced pain. Despite the major negative impact that severe pain in chronic OA has on quality of life and health care management, we only poorly understand origins of pain in OA, the molecular mechanisms driving the pathology, and the way to effectively cure OA. Many cases eventually require joint replacement with a prosthesis which is costly, and the limited functional life of prostheses (~10 y) can make a second replacement necessary. These factors increase both the overall cost of treatment and the risk for associated morbidity. Significantly, surgical procedures to address the condition typically do not result in a pain-free cure. Our central hypothesis is that activation of Flt1 (vascular endothelial growth factor receptor-1) is the major driver of joint pain transmission by plasticity of peripheral (sensory neurons) and central glial activation; Flk1 (vascular endothelial growth factor receptor-2) is primarily responsible for cartilage degeneration during the OA progression, thus, simultaneous inhibition of Flt1 and Flk1 by pazopanib, an FDA-approved small molecule anti-cancer drug, will act as an ideal OA disease-modifying drug (OADMD) with immediate reduction of joint pain and gradually cartilage regeneration. The findings of our proposed research will take the field of OA research a giant step forward: in the short term, by increasing our mechanistic understanding of the causes and progression of OA, and by developing a novel strategy for treating OA and joint pain effectively and safely in our pre-clinical OA animal model; and, in the longer term, by providing a rationale for clinical trials to test pazopanib to treat OA patients.

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