2022 Fiscal Year Final Research Report
Development of combination therapy of tanezumab and intra-articular injection in an osteoarthritic rat model
Project/Area Number |
18K16642
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Hokkaido University |
Principal Investigator |
Iwasaki Koji 北海道大学, 医学研究院, 特任助教 (40771895)
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Keywords | 神経成長因子 / 変形性膝関節症 / 保存治療 |
Outline of Final Research Achievements |
Knee osteoarthritis (OA) was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100μg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100μg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA. Keywords:
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Free Research Field |
変形性膝関節症
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Academic Significance and Societal Importance of the Research Achievements |
変形性膝関節症(OA)は高齢者に多く発症し,その治療は高齢化が進む日本の医療において重要である.膝OAに対する保存治療には,NSAIDS,麻薬などが用いられているが,その効果の程度,副作用から除痛効果が強く安全性の高い薬剤が期待されている.抗NGF抗体の全身投与治療は,優れた除痛効果をもたらすが,膝OAの増悪を引き起こすことが報告されている.本研究の結果,膝OAラットにおいて抗NGF抗体の関節注射治療は,全身投与と比べ少量の抗NGF抗体で除痛効果が得られ,膝OA増悪を惹起しないことが明らかになり,有効な膝OA治療方法としての可能性が示唆された.
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