Spontaneous MRL/lpr Model of SLE
Systemic Lupus Erythematosus (SLE) is a chronic, inflammatory, systemic autoimmune disease affecting multiple organs systems. Common characteristics of SLE include kidney disease, skin eruptions, joint pain, pulmonary, and neuropsychiatric complications. Vium offers a commonly used murine model of lupus (MRL/MpJ-Faslpr (MRL/lpr)) against which to validate the efficacy of potential therapeutic compounds.
The MRL/lpr mice spontaneously develop disease that closely mimics human SLE pathologies including nuclear autoantibody production, enlargement of lymph nodes, skin lesions, hypergammaglobulinemia (increased IgG levels), proteinuria, and kidney failure (2-4). In this model, various immune cell populations (5-7), including B and T cells, contribute to the pathogenesis of the disease.
Vium Digital Study Metrics
Common features of SLE in both MRL/lpr and patients include joint pain and kidney disease. MRL/lpr mice display a significant decrease motion as disease develops and progresses (see Fig. 1A). Motion metrics provide an additional measure against which to assess the disease state of mice.
Optional conventional metrics
- Proteinuria score (1/week)
- Anti-dsDNA titration (1/month)
- Organ histopathology (study end)
Breathing Rate: Most patients with SLE show signs of lung involvement, including dyspnea. MRL/lpr mice display elevated breathing rates as disease progresses (Fig. 1B). Frequent assessment of breathing rates allows researchers to compare breathing rates across the course of the disease as well as focus on changes before and after therapeutic interventions.
Lupus Model - Disease vs Control Phenotype
Animals are monitored in Vium Smart Houses from arrival at the age of 6 weeks. Conventional weekly measures of proteinuria and body weights can be collected to follow disease onset and progression. Monitoring continues until the end of study (generally 13-15 weeks later). Organ weights are collected and histopathology performed to score the severity of the disease. Blood collection may also be performed at regular intervals and end of study to assess level of biomarkers such as anti-dsDNA.
Prior to treatment, subjects are randomized into groups ensuring both body weight, motion, and proteinuria scores are similar between all groups.
For prophylactic studies, test compounds are administered (SC, PO, IP or IV) beginning between 8-10 weeks of age, prior to disease onset. For therapeutic studies, test compounds are administered (SC, PO, IP or IV) after disease onset, which is defined by proteinuria score equal or greater than 2 (>100 mg/dL).
Treatment efficacy is analyzed using Vium metrics (and option conventional measures) that assess:
- 24/7 Motion Activity (Nightly, daily and circadian motion)
- Breathing rate (Daily and weekly averages)
- Proteinuria scores
- Blood Biomarkers: anti-dsDNA
- Tissue histology
- Lymphoadenopathy and skins lesions assessment
- Spleen and Lymph nodes weights
Standard of Care Drugs
The following positive control therapeutics may be used:
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