Membranoproliferative Glomerulonephritis (MPGN) is a rare disorder that is immune mediated and affects the kidneys. It is marked by the overgrowth of cells of the kidney's filtration system and the deposition of immune complexes beneath the cell layer ordered to the glomerular membrane. Protheragen provides drug and therapeutic development services for rare kidney diseases, including MPGN.
Introduction to Membranoproliferative Glomerulonephritis
MPGN is an autoimmune condition marked by inflammation of the kidney glomerulus and is often paired with the kidney diseases of glomerular hypertension and diabetic nephropathy. MPGN, which derives its name from a combination of glomerular lesions and membranous nephritis, is now defined based on its dominant pathophysiological drivers, which center on the deposits of immune complexes and/or dysregulation of the complement system. This has facilitated the description of primary immune complex-mediated MPGN (IC-MPGN) and C3 Glomerulonephritis (C3G), both of which result from uncontrolled complement activation.
Pathogenesis of Membranoproliferative Glomerulonephritis
Fig.1 The complement cascade. (Noris, Daina and Remuzzi, 2023)
In MPGN, pathogenesis is heterogeneous, arising from inappropriate immune mechanisms giving rise to glomerular damage. In IC-MPGN, immune complex deposition in the glomeruli elicits inflammatory cascades. In C3G, the driving force is pathological control of the alternative complement pathway and disproportionate response and superabundance of C3 (C3b, C3dg) and its degradation products in the glomeruli. This form of complement dysregulation may be acquired, such as through autoantibodies C3 nephritic factor, or genetically through mutations in complement regulatory proteins of Factor H, Factor I, or Factor B. This chronic inflammatory response gives rise to the proliferation of mesangial and endothelial cells, resulting in thickening of the glomerular basement membranes. This will lead to glomerulosclerosis and interstitial fibrosis, with the progressive loss of renal function.
Therapeutic Development for Membranoproliferative Glomerulonephritis
| Drug/Therapy Name |
Target/Approach |
Key Mechanism & Findings |
Current Stage |
| Eculizumab |
C5 protein |
Blocks C5 cleavage and MAC formation; reduces complement activation in DDD models |
Phase II |
| Compstatin analogs (e.g., Pegcetacoplan) |
C3 protein |
Selective C3 cleavage blockade; reduces proteinuria in primate models |
Preclinical |
| Anti-C3NeF monoclonal antibody |
C3 convertase autoantibody |
Inhibits complement dysregulation; prevents C3 consumption in vitro |
Preclinical |
| Recombinant Factor H protein |
Factor H protein |
Corrects FH deficiency; reduces renal deposition in animal models |
Preclinical |
| Fresolimumab |
TGF-β1 |
Suppresses fibrotic signaling; decreases collagen deposition in MPGN models |
Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen specializes in developing advanced disease models for membranoproliferative glomerulonephritis and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse immunological and genetic impacts that lead to MPGN.
Therapeutic Development Platform for Membranoproliferative Glomerulonephritis
Protheragen combines deep expertise in kidney immunology, complement biology, and the genetics of glomerular diseases with advanced molecular and cellular technologies to address the multifaceted mechanisms leading to MPGN.
Disease Models Development for Membranoproliferative Glomerulonephritis
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of membranoproliferative glomerulonephritis. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the immunological and complement dysregulation that cause MPGN, supporting extensive drug discovery and mechanism-based investigations focused on glomerular inflammation and repair.
Cell-based & Organoid Models
- Human Glomerular Endothelial Cells
- Human Podocytes
- Human Mesangial Cells
- iPSC-Derived Kidney Organoids
- Co-culture models of glomerular cells
Animal Models Development
- Complement-Dysregulation Mice
- Factor H Mutations Mice
- Immune Complex-Mediated Glomerulonephritis Models
- Thy-1 Nephritis Rat Model
- NZB/W F1 mice
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Metabolic Stability Assay
- Plasma Protein Binding
- Renal Tubular Epithelial Cell Uptake & Efflux
- Drug-Transporter Interaction Profiling
- Cellular Permeability
In Vivo Pharmacokinetics Services
- Systemic Pharmacokinetics
- Kidney Tissue Distribution and Retention
- Renal Clearance and Excretion Studies
- Urinary Metabolite Profiling
- Blood-to-Plasma Ratio
Protheragen provides integrated preclinical development solutions specifically designed for research in rare immune-mediated kidney diseases like membranoproliferative glomerulonephritis. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.
If you are interested in our services, please don't hesitate to contact us.
References
- Noris, M., E. Daina, and G. Remuzzi. "Membranoproliferative Glomerulonephritis: No Longer the Same Disease and May Need Very Different Treatment." Nephrol Dial Transplant 38.2 (2023): 283-90.
- Yu, S. M., et al. “Membranoproliferative Glomerulonephritis Pattern of Injury.“ Adv Kidney Dis Health 31.3 (2024): 216-22.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
