Primary Hyperoxaluria
Primary hyperoxaluria, a rare hereditary disorder, is characterized by mutations in genes responsible for the metabolism of glyoxylate, a vital precursor of oxalate. Our company excels in the field of rare disease diagnostics and therapeutics development, particularly in areas like primary hyperoxaluria, by offering a wide range of comprehensive services tailored to meet the needs of researchers and customers.
Overview of Primary Hyperoxaluria
Primary hyperoxaluria is a complex hereditary disorder that stems from mutations in genes related to the metabolism of glyoxylate. Individuals with primary hyperoxaluria often experience the combined effect of oxalate and calcium forming crystals in the kidneys, leading to kidney stone formation, urinary tract obstruction, and complications. Prolonged oxalate crystal accumulation can progressively damage the kidneys, ultimately leading to chronic kidney disease (CKD) and, in severe cases, end-stage renal disease (ESRD).
Fig.1 Causes of hyperoxaluria. (Demoulin, N., et al., 2022)Pathogenesis of Primary Hyperoxaluria
Primary hyperoxaluria is a rare genetic disorder wherein oxalate, a substance usually eliminated through the kidneys, accumulates excessively due to genetic mutations. This accumulation leads to the formation of insoluble crystals, primarily in the kidneys, potentially causing kidney stone development. Types 1, 2, and 3 of primary hyperoxaluria are linked to mutations in specific genes - AGXT, GRHPR, and HOGA1, respectively, disrupting normal glyoxylate breakdown and resulting in oxalate overproduction.
Fig.2 Strategies for molecular therapy in primary hyperoxaluria. (Hoppe, B., and Martin-Higueras, C., 2022)Diagnostics Development of Primary Hyperoxaluria
Diagnosis of primary hyperoxaluria involves the use of spectrophotometric, chromatographic, or enzymatic methods to quantify oxalate levels accurately, assess kidney function, and perform genetic testing by advanced sequencing technologies to confirm the specific mutations associated with the condition.
Therapeutics Development of Primary Hyperoxaluria
| Agents | Types | Mechanism | Research Phase |
|---|---|---|---|
| Stiripentol | Small molecule inhibitor | Inhibition of hepatic lactate dehydrogenase | Phase III trials |
| Nedosiran | Small interfering RNA | Inhibition of hepatic lactate dehydrogenase | Approval |
| Lumasiran | Small interfering RNA | Lumasiran targets GO, reducing the production of glyoxylate | Approval |
| Oxalobacter formigenes | Bacterium | Degrade oxalate in the intestine | Phase II trials |
| CRISPR/Cas9 | Genome editing tool | Induce insertions and deletions (indels) in the genome, such as GO or LDH | Preclinical research |
Our Services
Through cutting-edge technologies and innovative approaches, we ensure that our services are at the forefront of rare disease research. We have animal models and therapeutic development platform which can help you address the specific needs and challenges associated with primary hyperoxaluria.
Therapy Development Platforms
Animal Models of Primary Hyperoxaluria
Animal models contribute significantly to our understanding of primary hyperoxaluria and testing potential therapeutics. Our company can provide a variety of animal models to help you investigate the underlying mechanisms, evaluate therapeutic strategies, and assess their safety and efficacy.
Chemical-induced models involve exposing animals to specific substances that induce the characteristics of primary hyperoxaluria. These substances are typically metabolized into oxalate, leading to hyperoxaluria.
Optional Models: Ethylene glycol-induced model; Glyoxylate-induced model, etc.
Genetic engineering models involve modifying the genes responsible for glyoxylate metabolism by gene editing techniques such as CRISPR/Cas9 to replicate the genetic defects seen in primary hyperoxaluria.
Optional Models: Agxttm1Ull model; Grhprem2Gpt model, etc.
Our commitment to excellence and customer satisfaction sets us apart in the industry, making us a trusted partner for those seeking solutions to rare diseases. We offer comprehensive services including pharmacokinetic studies and drug safety evaluation to both researchers and customers, to support groundbreaking research efforts.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Hoppe, Bernd, and Cristina Martin-Higueras. "Improving Treatment Options for Primary Hyperoxaluria." Drugs 82.10 (2022): 1077-1094.
- Demoulin, Nathalie et al. "Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review." American journal of kidney diseases: the official journal of the National Kidney Foundation 79.5 (2022): 717-727.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.