Idiopathic Membranous Nephropathy
Idiopathic membranous nephropathy (IMN) is a persistent autoimmune disorder that impacts renal function. As a distinguished CRO specializing in autoimmune disease therapeutics, our organization is resolutely focused on the development of pioneering drugs and therapies for the therapeutics of IMN.
Overview of Idiopathic Membranous Nephropathy
Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. IMN is characterized by the deposition of immune complexes, primarily IgG and complement component C3, along the glomerular basement membrane. This deposition leads to the thickening of the membrane, impairing its function and resulting in proteinuria, hypoalbuminemia, edema, and, in some cases, progressive renal damage.
The primary target antigen is phospholipase A2 receptor (PLA2R), which is expressed on podocytes in the kidneys. Other potential antigens, such as thrombospondin type-1 domain-containing 7A (THSD7A), have been identified in a subset of IMN cases. The binding of autoantibodies to these antigens triggers an immune response, leading to the formation of immune complexes that deposit in the glomerular basement membrane.
Fig.1 Mechanisms of kidney injury in membranous nephropathy (MN). (Ueda T., et al., 2021)
Therapeutics Development for Idiopathic Membranous Nephropathy
Immunosuppressants, including cyclosporine, tacrolimus, and mycophenolate mofetil (MMF), are often used in combination with corticosteroids for more resistant cases of IMN. These agents suppress the immune response and reduce the production of autoantibodies, leading to improved renal outcomes. In addition, rituximab, a monoclonal antibody targeting CD20 antigen on B cells, has emerged as a promising therapy for IMN. By depleting B cells, rituximab disrupts the production of autoantibodies and dampens the immune response.
With our state-of-the-art technology platform, we are firmly dedicated to pioneering groundbreaking therapeutic solutions for idiopathic membranous nephropathy (IMN). We invite you to explore further details by clicking on the link provided below.
Our Services
Through our all-inclusive therapy development service, we are fully equipped to cater to all your requirements. Our comprehensive approach ensures that we can address every aspect of your therapy development needs, providing a tailored solution that meets and exceeds your expectations.
In conjunction with our diagnostics and therapeutic development services, we take pride in offering comprehensive IMN disease model development services. Our expertise in this area allows us to create robust animal models and diverse in vitro models. These advanced models provide a valuable platform for studying the intricate mechanisms underlying IMN pathogenesis, evaluating the effectiveness of potential therapeutic interventions, and identifying novel targets for therapeutic development.
Heymann nephritis model involves the injection of renal tubular antigens, such as megalin and cubilin, into animals, resulting in the production of antibodies against these antigens. These antibodies then bind to the corresponding antigens in the renal tubules, leading to complement activation and immune complex deposition.
Heymann Nephritis Models
In this model, animals are immunized with dipeptidyl peptidase IV (DPPIV), leading to the production of antibodies against this enzyme. Subsequent injection of the immune serum into murine animals results in the deposition of immune complexes, primarily composed of IgG, within the glomeruli.
Anti-Dipeptidyl Peptidase IV Models
To generate an IMN animal model, animals undergo immunization with APA. This prompts the production of antibodies specifically targeting this enzyme. Following the immunization phase, animals receive injections of the immune serum, leading to the deposition of immune complexes within the glomeruli.
Anti-Aminopeptidase A (APA) Models
Thrombospondin type-1 domain-containing 7A (THSD7A) has been identified as a target antigen in a subset of IMN cases. Our company provides specialized services for the development of the THSD7A-associated MN model, enabling researchers to study the pathogenesis of IMN associated with THSD7A antibodies.
THSD7A-Associated MN Models
Animals are injected with C-BSA, which has a positive isoelectric point. This leads to the development of proteinuria and nephrotic syndrome resembling IMN. Immunofluorescence and electron microscopy analyses reveal immune complex deposition and structural changes in the glomerular basement membrane.
Cationic Bovine Serum Albumin (C-BSA) Models
This model is based on the non-collagen 1 domain of human α3 (IV) collagen, known as α3NC1, which is a component of the glomerular basement membrane (GBM). The α3NC1 has a higher isoelectric point, and it is hypothesized to promote GBM deposition, similar to the mechanism observed in the C-BSA model.
Anti-α3NC1 Mouse Models
In the APN model, mice are injected with murine podocytes as antigens, leading to the production of antibodies against these antigens. The immune serum containing these antibodies is then injected back into murine animals, resulting in large amounts of proteinuria and the deposition of immune complexes.
Anti-Podocyte Nephritis (APN) Models
Cell-based models play a vital role in the evaluation of potential therapeutics. Our company offers comprehensive cell-based model development services tailored specifically for IMN therapy development, including anti-THSD7A antibody-induced podocyte model and zymosan-activated serum (ZAS)-induced podocyte model.
By differentiating iPSCs into kidney organoids, we can study the complex interplay between various cell types within the glomerulus, including podocytes, mesangial cells, and endothelial cells. In addition, our company also offers co-culture models that allow for the study of cell-cell interactions involved in IMN pathogenesis.
Our company offers comprehensive preclinical research services for IMN therapy development. We conduct in-depth studies to evaluate the safety, efficacy, and pharmacokinetics of potential drug candidates. If our comprehensive suite of services has sparked your interest, we wholeheartedly encourage you to connect with us without any hesitation.
Reference
- Ueda Tomohiro, et al. "Current understanding and future perspectives of interstitial cystitis/bladder pain syndrome." International Neurourology Journal 25.2 (2021): 99.