Amyloid Light-chain Amyloidosis (AL-amyloidosis)
Light Chain Amyloidosis (AL) is a severe and rare condition that occurs when abnormal proteins, known as light chains, are produced by plasma cells in the bone marrow. Specialized drug and therapy development services are essential to enhance AL-amyloidosis research. Our company takes the lead in providing comprehensive AL-amyloidosis drug and therapy development solutions.
Introduction to AL-amyloidosis
Light chain amyloidosis is a systemic disease caused by the misfolding of proteins, characterized by the deposition of abnormal immunoglobulin light chains as insoluble fibrillar aggregates. These insoluble fibrils accumulate in various tissues, leading to organ dysfunction and, ultimately, death in individuals. It is estimated to occur in approximately 1 out of every 100,000 to 150,000 people per year globally.
Pathogenesis of AL-amyloidosis
The pathogenesis of AL amyloidosis involves the abnormal production and accumulation of light chain proteins, typically produced by clonal plasma cells. A common characteristic of these proteins is their tendency to form β-pleated sheets arranged in an anti-parallel fashion, creating rigid, non-branching fibrils resistant to proteolytic digestion. These fibrils infiltrate human organs, causing mechanical damage and localized oxidative stress.
Fig.1 Pathophysiology of amyloid light chain (AL) amyloidosis illustrating three fundamental mechanisms. (Grogan, Martha, et al., 2017)Diagnostics Development of AL-amyloidosis
Diagnosing AL amyloidosis entails identifying irregular light chains and amyloid deposits within tissues, employing a combination of laboratory analyses, imaging techniques, and biopsies. This comprehensive assessment includes evaluating symptoms such as fatigue and edema, conducting serum and urine tests to measure light chain levels, and performing biopsies to confirm the presence of amyloid deposits. Imaging studies and genetic testing help assess organ involvement and differentiate AL amyloidosis from other types, with bone marrow examination checking for plasma cell abnormalities, aiming for early, accurate diagnosis and better therapy outcomes.
Therapy Development of AL-amyloidosis
Antibodies targeting amyloid fibrils or precursor proteins have shown promise in enhancing the clearance of amyloid deposits from organs. Drugs like daratumumab, a monoclonal antibody against CD38 expressed on plasma cells, have been effective in reducing the burden of clonal plasma cells and amyloid deposits.
Chimeric Antigen Receptor (CAR) T-Cell Therapy, a cutting-edge approach involving the genetic modification of an individual's T cells to target specific proteins on cancer cells, is currently under investigation for its potential in targeting clonal plasma cells responsible for amyloid protein production.
Our Services
In the dynamic field of diagnostics for AL amyloidosis, our company is a leading innovator, consistently pushing the boundaries of technology. Our company possesses state-of-the-art instrumentation alongside a team of highly skilled technical professionals with rich expertise, forming the cornerstone of our expertise.
Platforms of AL-amyloidosis Therapy Development
Animal Models of AL-amyloidosis
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Induced Animal Models | |||
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| Our company specializes in developing induced animal models that faithfully replicate the pathology and immunological features of AL-amyloidosis. AEF, derived from amyloid fibrils, can induce amyloidosis in susceptible mouse strains, such as CBA/J mice. | |||
| Optional Models | Murine AA Model Induced by Amyloid-Enhancing Factor (AEF) | ||
| Genetically Engineered Models | |||
| At our company, we specialize in developing genetically engineered models for scientific research. Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human AL-amyloidosis. | |||
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| Optional Species | Mice, Rats, Others | ||
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways, proteasome pathways, and molecular targets. If you are interested in our services, please don't hesitate to contact us for detailed information and a formal quotation.
References
- Grogan, M., et al., "Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response." Heart (2017). 103(14): p. 1065-1072.
- Falk, R.H., et al., "AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy." J Am Coll Cardiol (2016). 68(12): p. 1323-1341.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.