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| Repetitive application of Serp-1 produces no obviously toxic effects. (A) Changes of body weight before and after experiments were measured and calculated (n = 5 for control group, n = 9 for Serp-1 group. *P < 0.05). (B) Histochemical analysis of eye cross-sections shows reduced rates of inflammatory cell infiltration and swelling of the cornea in Serp-1 treated mice. Enlarged images of the corneal region of two mice visibly show more swelling and a higher presence of inflammatory cells in the control mice. Inflammatory cell nuclei are stained by the deep-purple spots marked with white triangles in the light pink stromal layer of the cornea.

| Repetitive application of Serp-1 produces no obviously toxic effects. (A) Changes of body weight before and after experiments were measured and calculated (n = 5 for control group, n = 9 for Serp-1 group. *P < 0.05). (B) Histochemical analysis of eye cross-sections shows reduced rates of inflammatory cell infiltration and swelling of the cornea in Serp-1 treated mice. Enlarged images of the corneal region of two mice visibly show more swelling and a higher presence of inflammatory cells in the control mice. Inflammatory cell nuclei are stained by the deep-purple spots marked with white triangles in the light pink stromal layer of the cornea.

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Purpose: Chemical corneal injuries carry a high morbidity and commonly lead to visual impairment. Here, we investigate the role of Serp-1, a serine protease inhibitor, in corneal wound healing. Methods: An alkaline-induced corneal injury was induced in 14 mice. Following injury, five mice received daily topical saline application while nine mice re...

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Context 1
... first checked mouse body weight change after Serp-1 injection. While the mice receiving saline gained body weight, we did observe Serp-1 treatment group had slight reduction of body weight ( Figure 4A). However, when we checked major organs of the mice treated with Serp-1, we didn't observe pathologic inflammatory changes as result of the use of Serp-1 ( Figure 4B). ...
Context 2
... the mice receiving saline gained body weight, we did observe Serp-1 treatment group had slight reduction of body weight ( Figure 4A). However, when we checked major organs of the mice treated with Serp-1, we didn't observe pathologic inflammatory changes as result of the use of Serp-1 ( Figure 4B). Thus, further studies will be required to identify the cause of slight body weight loss after repetitive administration of Serp-1 protein in mice. ...
Context 3
... first checked mouse body weight change after Serp-1 injection. While the mice receiving saline gained body weight, we did observe Serp-1 treatment group had slight reduction of body weight ( Figure 4A). However, when we checked major organs of the mice treated with Serp-1, we didn't observe pathologic inflammatory changes as result of the use of Serp-1 ( Figure 4B). ...
Context 4
... the mice receiving saline gained body weight, we did observe Serp-1 treatment group had slight reduction of body weight ( Figure 4A). However, when we checked major organs of the mice treated with Serp-1, we didn't observe pathologic inflammatory changes as result of the use of Serp-1 ( Figure 4B). Thus, further studies will be required to identify the cause of slight body weight loss after repetitive administration of Serp-1 protein in mice. ...

Citations

... Treatment with purified native Serp-1 has demonstrated both acute and long-term efficacy in modulating inflammation in a wide range of inflammatory disorders and injuries, including atherosclerosis, transplant, wound healing, and spinal cord injury [39][40][41][42]. More recently, a modified Serp-1 protein, PEGSerp-1, with a longer halflife (~8 h), was shown to reduce inflammation and fibrosis in healing corneal wounds, and reduced macrophage invasion of alveoli in a mouse model of diffuse alveolar hemorrhage [43][44][45]. Based on these previous studies, we examined whether the pegylated version of the viral Serp-1 protein, PEGSerp-1, would ameliorate the chronic inflammatory pathology of DMD. ...
... We examined whether a pegylated version of the Myxoma virus serpin, Serp-1, would ameliorate the chronic inflammatory environment in DMD mdx /Utrn −/− mice. This protein has been shown to induce an anti-inflammatory response in wound healing, transplants, and other acute injuries without any demonstrated increase in adverse effects in multiple animal models and in one Phase IIa clinical trial [39][40][41][42][43][44][45]52,53]. Systemic PEGSerp-1 treatment of DKO mice significantly decreased muscle fibrosis and the number of infiltrating M1 pro-inflammatory macrophages. ...
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Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characterized by muscle weakness and wasting during early childhood, and loss of ambulation and death by early adulthood. Chronic inflammation due to myofiber instability leads to fibrosis, which is a primary cause of loss of ambulation and cardiorespiratory insufficiency. Current standard of care focuses on reducing inflammation with corticosteroids, which have serious adverse effects. It is imperative to identify alternate immunosuppressants as treatments to reduce fibrosis and mortality. Serp-1, a Myxoma virus-derived 55 kDa secreted glycoprotein, has proven efficacy in a range of animal models of acute inflammation, and its safety and efficacy has been shown in a clinical trial. In this initial study, we examined whether pegylated Serp-1 (PEGSerp-1) treatment would ameliorate chronic inflammation in a mouse model for Duchenne muscular dystrophy. Our data revealed a significant reduction in diaphragm fibrosis and increased myofiber diameter, and significantly decreased pro-inflammatory M1 macrophage infiltration. The M2a macrophage and overall T cell populations showed no change. These data demonstrate that treatment with this new class of poxvirus-derived immune-modulating serpin has potential as a therapeutic approach designed to ameliorate DMD pathology and facilitate muscle regeneration.