Orthopaedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, College of Veterinary Medicine, Colorado State University, Fort Collins, CO.
UNC Gene Therapy Center, University of North Carolina, Chapel Hill, NC.
J Am Vet Med Assoc. 2024 Apr 22;262(S1):S109-S120. doi: 10.2460/javma.24.02.0078. Print 2024 Jun 1.
To evaluate the effects of a gene transfer approach to IL-1β inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem.
16 horses were utilized for the study.
All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra or saline in the osteoarthritis joint. Horses were evaluated over 70 days clinically (lameness, imaging, and biomarker analysis) and euthanized at 70 days and evaluated grossly, with imaging and histopathology.
The following findings were statistically significant. Injection of scAAVIL-1ra resulted in high synovial fluid levels of IL-1ra (0.5 to 9 μg/mL) throughout the duration of the experiment (70 days). Over the duration, we observed scAAVIL-1ra to improve lameness (lameness score relative improvement of 1.2 on a scale of 0 to 5), cause suppression of prostaglandin E2 (a relative decline of 30 pg/mL), and result in histological improvement in articular cartilage (decreased chondrocyte loss and chondrone formation) and subchondral bone (less osteochondral splitting and osteochondral lesions). Within the synovial membrane of scAAVIL-1ra-treated joints, we also observed perivascular infiltration with CD3-positive WBCs, suggesting lymphocytic T-cell perivascular infiltration commonly observed with viral transduction.
These data provide support for further evaluation and optimization of scAAVIL-1ra gene therapy to treat equine osteoarthritis.
使用携带白细胞介素受体拮抗剂转基因盒的自我互补型腺相关病毒（scAAVIL-1ra）评估 IL-1β 抑制的基因转移方法在关节损伤的马骺软骨芯片片段模型中的效果，因为马的创伤后骨关节炎与人非常相似，是一个重大的临床问题。
16 匹马用于该研究。
所有马的一只腕中关节均通过关节镜诱导骺软骨芯片片段，而对侧关节为假手术。8 匹马在骨关节炎关节中接受 scAAVIL-1ra 或盐水注射。通过临床（跛行、影像学和生物标志物分析）和 70 天时安乐处死并进行大体评估、影像学和组织病理学评估来评估马 70 天。
以下发现具有统计学意义。注射 scAAVIL-1ra 导致整个实验期间（70 天）滑液中 IL-1ra 水平升高（0.5 至 9 μg/ml）。在整个过程中，我们观察到 scAAVIL-1ra 改善跛行（跛行评分相对改善 0 至 5 分的 1.2 分）、抑制前列腺素 E2（相对下降 30 pg/ml），并改善关节软骨（减少软骨细胞丢失和软骨形成）和软骨下骨（减少骺软骨分裂和骨软骨病变）的组织学。在 scAAVIL-1ra 治疗关节的滑膜中，我们还观察到血管周围浸润的 CD3 阳性白细胞，这提示常见于病毒转导的血管周围淋巴细胞 T 细胞浸润。
这些数据为进一步评估和优化 scAAVIL-1ra 基因治疗治疗马骨关节炎提供了支持。
