Dicarboxylic Aminoaciduria

Dicarboxylic Aminoaciduria (DA) is an uncommon inherited metabolic disorder distinguished by the disproportionate excretion of dicarboxylic amino acids due to a defect in their renal reabsorption. Protheragen is focused on developing therapeutic interventions for rare kidney disorders, including those with underlying metabolic transport defects. Here, we provide our tailored service solutions for dicarboxylic aminoaciduria.

Overview of Dicarboxylic Aminoaciduria

Dicarboxylic Aminoaciduria is a recessively inherited metabolic disorder with a dicarboxylic amino acid and aspartic aciduria. This disorder stems from a fundamental deficit in the renal tubular absorption of these amino acids. Broadly, it is often benign and asymptomatic, although presenting more severely is associated with the problem of risk. The disorder contributes to the risk of kidney stone formation because of the altered urinary composition. While rare, renal failure is possible, but there are long-term complications from recurrent stone disease than the acute complications. The precise prevalence in asymptomatic individuals is not known, but it is classified as a rare inborn error of metabolism.

Pathogenesis of Dicarboxylic Aminoaciduria

Fig.1 Transporters involved in glutamate and aspartate transport in kidney and intestine. (Camargo, Bockenhauer and Kleta, 2008)

Dicarboxylic Aminoaciduria is a disorder stemming from a malfunction in the renal proximal tubule's reabsorption process of dicarboxylic amino acids like glutamic and aspartic acid. This reabsorption process is facilitated by amino acid-specific transporters on the proximal tubule cell's apical membrane. Although not all DA cases have identifiable genes, most cases seem to stem from a mutation in the function, or a complete loss of, these transport proteins. This results in diminished renal reclamation of glutamic and aspartic acids and consequently, their excessive urinary excretion. Increased urinary concentration of these specific amino acids may contribute to abnormal urinary saturation, thereby increasing the risk of kidney stones.

Therapeutics Development for Dicarboxylic Aminoaciduria

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

Our Services

Protheragen specializes in developing advanced disease models for Dicarboxylic Aminoaciduria and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic and transport impacts that lead to DA and its associated renal manifestations.

Therapeutic Development Platforms for Dicarboxylic Aminoaciduria

• Small Molecule Drug
• Cell Therapy
• Gene Therapy

• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Disease Models Development for Dicarboxylic Aminoaciduria

Protheragen offers innovative and comprehensive disease models to advance the preclinical research of dicarboxylic aminoaciduria. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the tubular transport dysfunction and metabolic imbalances that cause DA, supporting extensive drug discovery and mechanism-based investigations focused on renal physiology and kidney stone formation.

Cell-based & Organoid Models

• Isogenic control iPSC line
• SLC1A1-deficient renal proximal tubule epithelial cells
• SLC1A1-deficient intestinal epithelial cells
• Neuronal glutamate transport-defective model

Animal Models

• Slc1a1 knockout mouse
• Proximal tubule-specific Slc1a1 KO mouse
• slc1a1 morpholino knockdown zebrafish
• Intestinal epithelial SLC1A1 KO mouse
• SLC1A1 point mutation rat

Drug Pharmacokinetics & Safety Evaluation Services

In Vitro ADME Services

• Renal Clearance Assay
• Drug-Transporter Interaction Screening
• Metabolic Stability Assay
• CYP Inhibition Screening
• Plasma Protein Binding

In Vivo Pharmacokinetics Services

• PK Studies in Renal Impairment Models
• Kidney Tissue Distribution Study
• Blood-to-Plasma Ratio
• Metabolite Profiling

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

Protheragen provides integrated preclinical development solutions specifically designed for research in rare genetic kidney disorders like Dicarboxylic Aminoaciduria. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.

If you are interested in our services, please don't hesitate to contact us.

References

1. Broer, S. "Amino Acid Transport across Mammalian Intestinal and Renal Epithelia." Physiol Rev 88.1 (2008): 249-86. Print.
2. Camargo, S. M., D. Bockenhauer, and R. Kleta. "Aminoacidurias: Clinical and Molecular Aspects." Kidney Int 73.8 (2008): 918-25.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.