In Vivo Model Development for Amyloidosis

Protheragen offers a comprehensive in vivo animal model development service tailored for Amyloidosis research and preclinical drug evaluation. Leveraging a diverse portfolio of established and custom models, we support pharmaceutical, biotechnology, and academic partners in advancing the understanding and therapeutic targeting of amyloid-related diseases. Our expertise spans multiple species and model types, enabling precise recapitulation of human amyloidosis pathologies and robust assessment of candidate treatments.

Amyloidosis encompasses a group of disorders characterized by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction. Accurate animal models are indispensable for unraveling disease mechanisms, identifying therapeutic targets, and evaluating the efficacy and safety of potential treatments. At Protheragen, we utilize both Drosophila melanogaster (fruit fly) and Mus musculus (mouse) models, employing a range of genetic, chemical, and protein-induced methodologies. Our models include transgenic strains expressing human amyloidogenic proteins such as TTR, APP, PSEN1, and IL6, as well as models induced by exogenous amyloid fibrils or amyloid enhancing factors. These systems closely mimic the molecular and pathological features of human amyloidosis, providing translational relevance and facilitating the development of effective therapies.

Genetic Models

Genetic models are created through the introduction or deletion of specific genes associated with amyloidosis, such as human transthyretin (TTR), amyloid precursor protein (APP), presenilin 1 (PSEN1), and interleukin-6 (IL6). These models include transgenic, knockout, and conditional expression systems in both mice (e.g., 5XFAD, TTR transgenic, IL6 transgenic, Ttr knockout) and Drosophila (neurons conditional transgenic TTR). The methodology involves targeted genetic modification to drive amyloid protein expression or ablation, resulting in spontaneous and progressive amyloid deposition. Key advantages include high construct validity, reproducibility, and the ability to model specific genetic forms of amyloidosis. These models are primarily used for mechanistic studies, therapeutic target validation, and preclinical efficacy testing.

Chemically-Induced Models

Chemically-induced models are established by administering amyloidogenic agents, such as synthetic beta-amyloid (1-42) peptides, to induce amyloid deposition in vivo. For example, immunosuppressed nude mice (nu/nu) can be treated with beta-amyloid peptides to rapidly develop amyloid pathology. The methodology allows for controlled induction of amyloidosis at specific time points. Advantages include rapid model establishment, flexibility in experimental design, and suitability for high-throughput screening. These models are widely applied in studies of amyloid clearance, acute toxicity, and evaluation of candidate therapeutics targeting amyloid aggregation.

Protein/Factor-Induced Models

This model type involves the induction of amyloidosis by introducing exogenous amyloid fibrils (such as human amyloid transthyretin fibrils) or amyloid enhancing factors into mice. The process accelerates amyloid deposition in target tissues, offering a model of secondary or acquired amyloidosis. The main advantages are the ability to mimic exogenous amyloid seeding and to study the kinetics of amyloid propagation. These models are particularly useful for investigating amyloid transmission, evaluating anti-amyloid therapies, and studying the impact of co-factors on disease progression.

Protheragen delivers a full-spectrum in vivo Amyloidosis model development and testing solution. Our services encompass model selection or custom generation, study design, animal husbandry, dosing and treatment administration, and comprehensive endpoint analysis. Key efficacy endpoints include amyloid burden quantification (histology, immunohistochemistry, Congo red and Thioflavin S staining), biochemical assays (ELISA for amyloid proteins, cytokines), behavioral and cognitive assessments (for neurological models), organ function evaluation, and survival analysis. Our analytical capabilities extend to advanced imaging (MRI, PET), mass spectrometry, and gene/protein expression profiling. Rigorous quality control measures are implemented throughout the process, including genetic validation of models, standardized protocols, and adherence to ethical and regulatory standards.

Partnering with Protheragen provides access to deep scientific expertise, validated and customizable amyloidosis models, and a commitment to delivering reliable, actionable data for your research and drug development programs. Our integrated approach accelerates discovery and de-risking of therapeutic candidates, supporting your goals from proof-of-concept to IND-enabling studies. Contact us today to discuss your project needs and discover how Protheragen can advance your amyloidosis research.