Development of molecular-targeted therapies for degenerative spondylosis and pain

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16613
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: University of Toyama
• Principal Investigator: MAKINO HIROTO 富山大学, 附属病院, 医員 (50816022)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 椎間板変性 / c-Fos / 疼痛 / 黄色靭帯肥厚

Outline of Final Research Achievements

Spondylosis is a common disease causes low back pain and spinal canal stenosis, and therefore, a radical treatment is required. We focused on the transcription factor c-Fos, which is located upstream of the matrix-degrading enzyme, and investigated the effects of a selective inhibitor of c-Fos/AP-1 (T-5224) on disc degeneration, disc-related pain and ligamentum flavum thickening. In a rat cocygeal disc puncture model, oral administration of T-5224 suppressed disc degeneration in imaging (X-ray, MRI) and histology fidings. In addition, T-5224 increased the threshold for pain in pain-related behaviour. In conclusion, it was suggested that selective c-Fos/AP-1 inhibition could prevent the progression of disc degeneration and related pain.

Free Research Field

脊椎外科

Academic Significance and Societal Importance of the Research Achievements

変形性脊椎症は、有病率の高い腰痛症や脊柱管狭窄症を引き起こし、結果として身体活動の低下を招くため、社会的な負担は大きい。しかし、現在においては対症療法が中心であり、椎間板変性や黄色靭帯肥厚を抑制する根本的治療法はない。本研究では、選択的c-Fos/AP-1阻害が、椎間板変性の進行を抑制し、疼痛に対しても抑制的に働くことを示した。このことより、脊椎の退行変化に対する新たな治療法の一つとなり得ることを示した。