Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J) mouse model of congenital muscular dystrophy.
Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J) mouse model of congenital muscular dystrophy.
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DOI：
10.1371/journal.pone.0065468
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Spurney CF
中科院分区：
文献类型：
--
作者：
Yu Q;Sali A;Van der Meulen J;Creeden BK;Gordish-Dressman H;Rutkowski A;Rayavarapu S;Uaesoontrachoon K;Huynh T;Nagaraju K;Spurney CF
先天性肌营养不良症是一组独特的疾病，在婴儿期或儿童期表现为肌无力，目前尚无治疗方法。其中一种形式 MDC1A 是层粘连蛋白 α-2 缺乏的结果，会导致严重虚弱、呼吸功能不全和过早死亡。细胞凋亡的修饰是这些患者的一种潜在治疗途径。 dy2J 小鼠每天通过口服强饲法用赋形剂、0.1 mg/kg 或 1 mg/kg omigapil 治疗，持续 17.5 周。未治疗的年龄匹配的 BL6 小鼠用作对照。收集功能、行为和组织学测量结果。与媒介物治疗的 dy2J 小鼠相比，用 omigapil 治疗的 dy2J 小鼠显示出呼吸频率改善（每分钟 396 至 402 次呼吸 vs. 371 次呼吸，p<0.03），并且与对照小鼠相似。在基线时或 17.5 周后，dy2J 和对照组之间的标准化前肢握力没有统计学差异，并且 dy2J 治疗组之间没有观察到显着差异。在 30-33 周龄时，与媒介物治疗相比，用 0.1 mg/kg omigapil 治疗的 dy2J 小鼠表现出明显更多的运动时间和更少的休息时间。 dy2J 小鼠在整个试验过程中表现出正常的心脏收缩功能。在试验结束时，与对照组相比，dy2J 小鼠的后肢最大力（p<0.001）和比力（p<0.002）显着降低。治疗之间的最大力或比力没有统计学上的显着差异。与载体相比，用0.1 mg/kg/天 omigapil 治疗的 dy2J 小鼠显示腓肠肌 (p<0.03) 和膈肌 (p<0.001) 纤维化百分比降低，与 1 mg/kg/天 omigapil 治疗小鼠相比膈肌 (p<0.013) 纤维化百分比降低。 Omigapil 治疗的 dy2J 小鼠表现出细胞凋亡减少。 Omigapil 疗法 (0.1 mg/kg) 可改善 dy2J 小鼠的呼吸频率并减少骨骼和呼吸肌纤维化。这些结果支持了 omigapil 在层粘连蛋白缺陷型先天性肌营养不良症患者中的使用的假定作用。
Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients. dy2J mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected. dy2J mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy2J mice (396 to 402 vs. 371 breaths per minute, p<0.03) and similar to control mice. There were no statistical differences in normalized forelimb grip strength between dy2J and controls at baseline or after 17.5 weeks and no significant differences seen among the dy2J treatment groups. At 30–33 weeks of age, dy2J mice treated with 0.1 mg/kg omigapil showed significantly more movement time and less rest time compared to vehicle treated. dy2J mice showed normal cardiac systolic function throughout the trial. dy2J mice had significantly lower hindlimb maximal (p<0.001) and specific force (p<0.002) compared to the control group at the end of the trial. There were no statistically significant differences in maximal or specific force among treatments. dy2J mice treated with 0.1 mg/kg/day omigapil showed decreased percent fibrosis in both gastrocnemius (p<0.03) and diaphragm (p<0.001) compared to vehicle, and in diaphragm (p<0.013) when compared to 1 mg/kg/day omigapil treated mice. Omigapil treated dy2J mice demonstrated decreased apoptosis. Omigapil therapy (0.1 mg/kg) improved respiratory rate and decreased skeletal and respiratory muscle fibrosis in dy2J mice. These results support a putative role for the use of omigapil in laminin deficient congenital muscular dystrophy patients.
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影响因子：
7.3
作者：
Sagot, Y;Toni, N;Kato, AC
通讯作者：
Kato, AC
DOI：
10.1073/pnas.97.16.9209
发表时间：
2000-08-01
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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通讯作者：
ENGVALL, E
影响因子：
2.8
作者：
Hayashi, YK;Tezak, Z;Arahata, K
通讯作者：
Arahata, K
影响因子：
4.8
作者：
Raben, N;Nagaraju, K;Plotz, P
通讯作者：
Plotz, P