Light Chain Amyloidosis

Light chain amyloidosis is an uncommon form of protein deposition disorder. It results from a B-cell clone responsible for the synthesis of a monoclonal light chain, thereby depositing in target organs and forming amyloid deposits. Carrying out diagnostics, therapeutics, and disease model development services is how we help researchers and pharmaceutical companies understand and treat these difficult diseases, and at Protheragen, we strive to understand and research the light chain amyloidosis disease with the help of our integrated services.

Introduction to Light Chain Amyloidosis

Light chain amyloidosis, also known as AL amyloidosis, is a rare and systemic disease form of amyloidosis. Available data suggests that it is reasonable to estimate that 8 to 12 new cases are diagnosed every year for every one million people. All organs can suffer from amyloid deposits except the central nervous system. The involvement of cardiac is the most common organ manifestation during amyloidosis and, when advanced, is the most prognostically unfavorable.

Cardiac involvement in AL amyloidosis individuals.

Fig.1 AL amyloidosis with cardiac involvement.
(De Michieli, L., et al., 2023)

Pathogenesis of Light Chain Amyloidosis

The underlying cause of systemic light chain amyloidosis is a clonal plasma cell or B-cell disease located in the bone marrow. Pathogenic plasma cells with specific cytogenetic and molecular features produce amyloidogenic light chains in excess. With the aid of matrix components, certain post-translational changes, and other factors in the surrounding environment, these light chains undergo a structural change that leads to the synthesis of amyloid fibrils.

In addition, the cytotoxic nature of the amyloidogenic light chain further aggravates the situation. This leads to organ dysfunction which is caused by organ architectural disruption together with the cytotoxic action of amyloidogenic light chains.

Fig.2 Molecular mechanisms of light chain amyloidosis. (Stelmach-Gołdyś, A., et al., 2022)

Therapeutics Development for Light Chain Amyloidosis

Drug Names	Mechanism of Action	Targets	NCT Number	Research Phase
Teclistamab	Minimizing the synthesis of pathogenic free light chains to avert injury to organs.	BCMA, CD3	NCT06649695	Phase II
Linvoseltamab	Redirects and activates CTLs for the scavenging of amyloidogenic proteins.	BCMA, CD3	NCT06292780	Phase I/II
ABBV-383	Facilitates immune response to remove the pathogenic proteins responsible for amyloidosis.	BCMA, CD3	NCT06158854	Phase I
NXC-201 CAR-T	Demonstrates complete response rates with the absence of any form of neurotoxicity in AL amyloidosis individuals.	BCMA	NCT06097832	Phase I
JNJ-79635322	A tri-specific antibody against the B-cell maturation antigen and G protein-coupled receptor class 5 member D.	BCMA, CD3, GPRC5D	NCT05652335	Phase I

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

With our integrated approach, we have a wealth of knowledge as well as a dedicated team of scientists and researchers specialized in AL amyloidosis who work on every project. This supports the works of researchers and pharmaceutical companies toward understanding and treating complex conditions through diagnostics, therapeutics, and disease model development services.

Therapeutic Development Services

Diverse Platforms

Animal Model Development Services

The development of new drugs hinges on animal models because they serve as vital instruments in comprehending the mechanisms of disease, evaluating new therapeutics and their vice, and carrying out preclinical trials. We specialize in developing such animal models for light chain amyloidosis and in so doing, we help researchers investigate the disease progression in a controlled preclinical model and assess the impact of novel therapy methodologies.

Induced Model Development

Administration of amyloidogenic light chain proteins into animals to induce deposition of amyloid in designated amyloid organs like the heart.

Optional models:

Human amyloidogenic light chains induced model
Recombinant amyloidogenic light chains induced model

Genetically Engineered Model

Transgenic strategy to increase the expression of human amyloidogenic light chains in animal models to reproduce systemic light-chain deposition.

Optional models:

CMV-lambda 6 transgenic model
Other models

Protheragen takes great pride in providing integrated preclinical services for AL amyloidosis. These services cover all aspects of disease research including pharmacodynamics, pharmacokinetics, and safety. We observe the highest quality and ethics in the execution of all our research services to make certain the outcome is dependable. For any inquiries concerning our services, feel free to reach out and request detailed information and our pricing guidelines.

References

De Michieli, Laura et al. "Light-chain cardiac amyloidosis for the non-expert: pearls and pitfalls." Internal and emergency medicine 18.7 (2023): 1879-1886.
Stelmach-Gołdyś, Agnieszka et al. "Physiology, Diagnosis and Treatment of Cardiac Light Chain Amyloidosis." Journal of clinical medicine 11.4 (2022): 911.

For research use only, not for clinical use.