Lowe Oculocerebrorenal Syndrome (OCRL)

Lowe oculocerebrorenal syndrome (OCRL) is a rare genetic disorder characterized by impairments in the eyes, brain, and kidneys. A mutation in the OCRL gene causes this disorder, resulting in significant health challenges. As a prominent rare kidney disorder research service provider, Protheragen excels in offering an all-inclusive one-stop service for OCRL drug development, which comprehensively addresses the entire drug development lifecycle.

Overview of Lowe Oculocerebrorenal Syndrome (OCRL)

The Lowe oculocerebrorenal syndrome (OCRL) is a rare disorder, being an X-linked multisystemic disorder, which is diagnosed with the presence of congenital cataracts, proximal renal tubular dysfunction, and intellectual disability. While the baby is born with ocular symptoms and severe muscular hypotonia, the incomplete renal Fanconi syndrome is often diagnosed much later in life. As of now, the estimations have placed OCRL's prevalence at 1 in 500,000.

Fig.1 Renal pathology in an individual with OCRL. (Zhang, Y., et al., 2021)

Pathogenesis of Lowe Oculocerebrorenal Syndrome (OCRL)

Lowe oculocerebrorenal syndrome (OCRL) is associated with genetic changes in the OCRL gene located on the X chromosome at Xq25-26, which synthesizes OCRL-1, an inositol polyphosphate 5-phosphatase. It is transported to the endosomes, trans-Golgi network, and endocytic clathrin-coated pits. The deficiency of this enzyme results in the loss of regulatory control of vesicular transport, which, in turn, may be critical for the development of the organ system dysfunction that is characteristically seen in Lowe syndrome.

Fig.2 The structure and function of OCRL-1. (Bökenkamp, A., and Ludwig, M., 2016)

Therapeutics Development for Lowe Oculocerebrorenal Syndrome (OCRL)

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 offers all-in-one research services tailored for OCRL therapeutic innovation to expedite the discovery and development processes. Our research and development solutions are integrated to address every stage of the drug development pipeline. We focus on the creation of diagnostics and therapeutics as well as disease model development. In the preclinical stage, we also offer profound pharmacokinetics and safety studies to confirm the safety and effectiveness of drug candidates prior to advancing further in the trials.

Therapeutic Development Platforms for OCRL

Disease Models Development for OCRL

For preclinical research purposes, precise and trustworthy disease models are important. To aid in screening for potential drug candidates and evaluating therapeutic efficacy, we develop and validate sophisticated OCRL models to help understand disease pathogenesis. Our modeling services comprise the creation and application of sophisticated kidney organoids and relevant animal models, as well as the development and application of cell-based models.

Cell-based & Organoid Models

• Primary cell model
• Patient-derived stem cell lines
• 3D renal proximal tubule on chip model
• Patient-derived kidney organoids
• And more

Animal Models Development

Employing advanced genetic engineering techniques to create animal models of OCRL.

• OCRL knockout mouse models
• Zebrafish models with OCRL mutations
• And more

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 is a professional leader in OCRL research and in rare kidney disease research more broadly. From disease modeling for OCRL in vitro assays and in vivo research to sophisticated preclinical testing, we offer streamlined, integrated services for therapeutic development. Contact us to learn how we can help you achieve your research goals so that your advanced therapeutics can push to the market.

References

1. Bökenkamp, Arend, and Michael Ludwig. "The oculocerebrorenal syndrome of Lowe: an update." Pediatric nephrology (Berlin, Germany) 31.12 (2016): 2201-2212.
2. Zhang, Yu et al. "Novel pathogenic OCRL mutations and genotype-phenotype analysis of Chinese children affected by oculocerebrorenal syndrome: two cases and a literature review." BMC medical genomics 14.1 (2021): 219.

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