Metabolic Liver Diseases
Protheragen provides preclinical research services for metabolic liver diseases, integrating targeted metabolomics profiling, gene/cell therapy development, and small-molecule drug optimization validated in disease-specific models, supporting collaborative efforts to advance precision therapies for genetic and metabolic hepatic disorders.
Disease Landscape & Clinical Challenges
- Clinical Challenges
Diagnostic delays, particularly in conditions like Wilson disease, often lead to irreversible organ damage due to nonspecific early symptoms. Current therapies, such as copper chelation or enzyme replacement, primarily manage symptoms but fail to address genetic root causes and may introduce long-term side effects.
Disease progression varies significantly even among patients with identical mutations, influenced by epigenetic and environmental factors, complicating prognosis. Additionally, ~70% of cases, including glycogen storage disorders, manifest in childhood, requiring urgent intervention to prevent life-threatening complications and highlighting the need for early, targeted therapies.
Fig1. Hepatic and extrahepatic manifestations associated with various liver diseases. (Gan, et al., 2025)- Genetic & Metabolic Characteristics
| Disease | Gene Defect | Metabolic Disruption | Key Biomarkers |
|---|---|---|---|
| Wilson disease | ATP7B | Copper accumulation | Low ceruloplasmin, high urinary copper |
| AATD | SERPINA1 | Z-AAT polymer aggregation | Serum AAT levels, liver Z-AAT deposits |
| GSD type I | G6PC | Impaired gluconeogenesis | Hypoglycemia, lactic acidosis |
| Tyrosinemia | FAH | Tyrosine toxicity | Succinylacetone in urine |
- Advances in Metabolic Liver Disease Research
Recent advancements in metabolomics and gene-editing technologies are driving targeted interventions for metabolic liver diseases. Innovations include CRISPR-based correction of pathogenic mutations, allele-specific siRNA therapies, and PEGylated enzyme replacements, alongside small-molecule modulators to restore metabolic pathways. These strategies emphasize precision medicine, addressing genetic root causes and systemic complications while tackling disease heterogeneity.
Fig2. Gene modification outcomes using genome editing tools. (Bryson, et al., 2017) Our Services
Protheragen supports translational research for metabolic liver disorders through integrated preclinical platforms, combining mechanistic insights with therapeutic development to accelerate drug discovery.
Disease Mechanism & Model Development
Our services integrate advanced metabolomic profiling to map pathway disruptions and identify therapeutic targets. We develop CRISPR-engineered models, such as gene-edited rodents and iPSC-derived hepatocytes, to recapitulate disease-specific mutations. Patient-derived organoids and 3D liver co-culture systems further enable phenotypic validation and biomarker discovery in human-relevant contexts.
Therapeutic Development & Optimization
We specialize in small-molecule drug discovery, including high-throughput compound screening and structure-guided design for enzyme modulators or metabolite regulators. For gene and RNA-based therapies, our platform optimizes AAV/LNP delivery systems for liver tropism, designs allele-specific siRNA/ASOs, and validates CRISPR-Cas9/base-editing strategies. All candidates undergo rigorous efficacy testing in disease-specific models, including organoids and humanized liver mice, to assess target engagement and functional rescue.
Translational Biomarker & Safety Assessment
Comprehensive safety profiling includes chronic toxicity studies in humanized models, immunogenicity risk evaluation for biologics, and pharmacokinetic/pharmacodynamic analyses. We deploy metabolomics-driven biomarker panels to monitor therapeutic response, off-target effects, and long-term outcomes. Customized assays, such as metabolic flux analysis and mitochondrial function assessments, further support mechanistic safety validation.
Metabolic liver diseases demand tailored therapeutic strategies that address their complex genetic and biochemical underpinnings. At Protheragen, we combine deep disease biology expertise with cutting-edge preclinical technologies to accelerate your drug development pipeline-from target validation to IND submission. If you are interested in our services or wish to know more information, please feel free to contact us at any time.
FAQs?
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Q: What types of metabolic liver diseases does your research target?
A: We focus on genetic and acquired metabolic liver disorders, including Wilson's disease and alpha-1 antitrypsin deficiency, which involve disruptions in hepatic metabolism and require targeted therapeutic strategies.
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Q: What is the typical timeline for metabolic pathway analysis projects?
A: Project duration depends on scope and complexity, but standard metabolic profiling studies typically require 2–4 months to complete, encompassing experimental design, data acquisition, and analytical reporting.
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Q: Do you support small-molecule drug development?
A: Yes, we provide integrated small-molecule drug development services, including structure-based design, synthetic optimization, and preclinical validation of efficacy and safety in disease-relevant models.
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Q: Which technologies are employed for metabolic studies?
A: Our platform utilizes advanced analytical methods such as mass spectrometry and nuclear magnetic resonance spectroscopy to deliver precise quantification of metabolites and pathway dynamics, ensuring robust mechanistic insights.
References
- Gan C.; et al. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther. 2025;10(1):33.
- Bryson TE.; et al. Nuclease-Mediated Gene Therapies for Inherited Metabolic Diseases of the Liver. Yale J Biol Med. 2017;90(4):553-566.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.