Biomarker Analysis Services
At Ace Therapeutics, we are at the forefront of innovative research and development, offering specialized biomarker services to accelerate the discovery and validation of novel therapeutics for iron overload disorders. Understanding the intricate mechanisms of iron metabolism is crucial for developing effective treatments, and our comprehensive biomarker panel provides critical insights into disease pathogenesis, drug efficacy, and patient response.
Iron overload, a condition characterized by excessive iron accumulation in the body, can lead to severe organ damage and life-threatening complications. The development of new drugs to combat this condition requires precise tools to monitor iron status, assess treatment efficacy, and identify patient populations most likely to benefit. Our cutting-edge biomarker services leverage a panel of key genetic and protein markers, each playing a vital role in iron homeostasis.
The foundation of effective therapeutic intervention lies in understanding the molecular underpinnings of disease. Our biomarker discovery services are designed to identify novel and robust indicators of iron overload status, progression, and therapeutic response.
Multi-Omics Approach: We leverage cutting-edge -omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to conduct unbiased, high-throughput screening. This allows for a comprehensive survey of biological systems to identify potential DNA, RNA, protein, or metabolite biomarkers associated with iron dysregulation, organ-specific iron accumulation, or pathways modulated by new therapeutic entities.
Candidate Validation and Prioritization: Following initial discovery, we employ rigorous bioinformatics analysis and targeted validation strategies to confirm the association of candidate biomarkers with iron overload pathophysiology or treatment outcomes. This includes preliminary screening in relevant preclinical models and human samples to select the most promising candidates for further development.
Once promising biomarkers are identified, the development of sensitive, specific, and reliable assays is paramount for their successful implementation in preclinical and clinical settings.
Diverse Technological Platforms: Our experienced team develops custom assays or adapts existing ones tailored to the unique characteristics of each biomarker and the specific requirements of your program. Our capabilities include:
Immunoassays: ELISA, Chemiluminescent Immunoassays (CLIA), multiplex bead-based assays for protein quantification.
Mass Spectrometry (LC-MS/MS): For highly sensitive and specific quantification of small molecules, peptides, and proteins, including challenging analytes like hepcidin.
Flow Cytometry: For cellular biomarker analysis, including receptor expression and intracellular markers.
Molecular Diagnostics: Quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS) for nucleic acid-based biomarkers, including gene expression analysis (e.g., HAMP, SLC40A1, TFRC, TMPRSS6, SLC11A2) and genetic variant detection.
Histopathology and Imaging: Immunohistochemistry (IHC) and other tissue-based assays for evaluating biomarker expression and localization in relevant tissues.
Rigorous Method Validation: All developed assays undergo stringent validation according to international regulatory guidelines (e.g., FDA, EMA). This comprehensive validation process assesses key performance characteristics, including sensitivity, specificity, accuracy, precision (intra- and inter-assay), linearity, range, robustness, and stability in relevant biological matrices, ensuring the generation of reliable and reproducible data for your studies.
Our analytical laboratories are equipped to perform precise and efficient biomarker analysis on a wide range of biological samples, supporting both preclinical research and clinical trials.
Sample Analysis: We routinely analyze diverse sample types, including blood, serum, plasma, urine, tissue biopsies (e.g., liver), and cellular extracts, employing optimized protocols to ensure sample integrity and data quality.
High-Throughput Capabilities: We offer both single-analyte and multiplexed analytical platforms. Multiplexing allows for the simultaneous measurement of multiple biomarkers from a small sample volume, providing a more comprehensive biological snapshot, increasing efficiency, and conserving precious samples. This is particularly valuable for assessing panels of iron metabolism markers like serum ferritin, transferrin saturation, soluble transferrin receptor, and hepcidin.
Our comprehensive services can be applied to a wide array of established and novel biomarkers relevant to iron overload. The following are key examples of biomarkers whose analysis is critical in this field and for which we offer robust assay solutions.
| Gene Target | Biological Function | Application as a Biomarker |
|---|---|---|
| Hepcidin Antimicrobial Peptide (HAMP) | Hepcidin is the master regulator of systemic iron homeostasis. Produced primarily by the liver, it controls iron absorption from the duodenum and iron release from macrophages by binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter. | Diagnostic/Prognostic: Serum hepcidin levels reflect body iron stores and erythropoietic iron demand. Low hepcidin is characteristic of most forms of hereditary hemochromatosis, while high hepcidin can indicate iron-refractory iron deficiency anemia or inflammation. Changes can indicate disease severity and progression. Pharmacodynamic: Monitoring hepcidin levels can assess the biological activity of drugs targeting iron metabolism, particularly those designed to modulate hepcidin expression or its interaction with ferroportin. |
| Solute Carrier Family 40 Member 1 (Ferroportin, SLC40A1) | Ferroportin is the only known iron exporter in vertebrates, responsible for releasing iron from cells (e.g., enterocytes, macrophages, hepatocytes) into the bloodstream. Its activity is post-translationally regulated by hepcidin. | Diagnostic/Prognostic: Mutations in SLC40A1 cause a form of hereditary hemochromatosis (Ferroportin Disease). Assessing ferroportin expression and function can be crucial for understanding disease mechanisms and predicting drug response, especially for therapies targeting the hepcidin-ferroportin axis. Target Engagement: For drugs directly targeting ferroportin, changes in its levels or cellular localization can serve as biomarkers of target engagement. |
| Transferrin Receptor (TFRC) | The transferrin receptor 1 (TfR1) is a transmembrane protein crucial for cellular iron uptake. It binds to iron-loaded transferrin (Tf) in the plasma and internalizes it, making iron available for cellular processes. Its expression is regulated by intracellular iron levels. | Diagnostic/Prognostic: Soluble transferrin receptor (sTfR) levels in the serum reflect total body TfR1 expression and are inversely correlated with iron stores, making sTfR a sensitive marker of iron deficiency and erythropoietic activity. In iron overload, sTfR may be less informative than ferritin or hepcidin but can help differentiate types of anemia or assess erythropoiesis. Pharmacodynamic: Changes in sTfR can indicate alterations in cellular iron uptake or erythropoietic demand in response to therapy. |
| Transmembrane Serine Protease 6 (TMPRSS6) | Also known as Matriptase-2, TMPRSS6 is a liver-specific transmembrane serine protease that plays a critical role in downregulating hepcidin expression. It does this by cleaving hemojuvelin (HJV), a co-receptor in the BMP/SMAD signaling pathway that induces hepcidin. | Diagnostic/Prognostic: Mutations in TMPRSS6 lead to iron-refractory iron deficiency anemia (IRIDA) due to inappropriately high hepcidin levels. Understanding TMPRSS6 activity is vital for diagnosing specific iron disorders. Pharmacodynamic/Predictive: For therapies aimed at modulating the TMPRSS6-HJV-hepcidin axis, measuring TMPRSS6 activity or downstream effects on hepcidin can serve as important pharmacodynamic biomarkers. Genetic variants in TMPRSS6 may also predict response to certain iron therapies. |
| Solute Carrier Family 11 Member 2 (SLC11A2) | Divalent Metal Transporter 1 (DMT1), also known as NRAMP2, is a key protein responsible for the absorption of dietary non-heme iron in the duodenum. It also plays a role in iron transport out of endosomes within cells following transferrin receptor-mediated endocytosis. | Diagnostic/Prognostic: Mutations in SLC11A2 can cause severe microcytic anemia with hepatic iron overload. Assessing DMT1 expression and function can be relevant for understanding specific iron absorption defects. Pharmacodynamic: For drugs that might affect intestinal iron absorption or intracellular iron trafficking, monitoring DMT1 expression or activity, or downstream markers of iron absorption, could be valuable. |
By integrating our advanced biomarker discovery, assay development, and analytical services, Ace Therapeutics provides a powerful resource to enhance the understanding of your compound's mechanism of action, demonstrate target engagement, and assess clinical efficacy in iron overload. We are committed to a collaborative approach, working closely with you to design and implement biomarker strategies that meet your specific research objectives and regulatory requirements.
Contact us to discuss how our expertise can propel your iron overload therapeutic development forward.
Make Order
Experimental Scheme
Implementation
Conclusion
Ace Therapeutics has a group of highly committed and skilled researchers with the objective to provide innovative preclinical contract research solutions to cope with kidney diseases.
We strives to accelerate the development of innovative therapies that address unmet medical needs.