Zellweger Spectrum Disorder (ZSD)
Zellweger spectrum disorder (ZSD) is a lethal autosomal recessive disorder caused by mutations in PEX genes. At Protheragen, we are committed to advancing the understanding and management of ZSD through cutting-edge therapeutic development and disease modeling services. Our goal is to provide end-to-end solutions for the entire process from ZSD therapeutic research to commercialization.
Overview of Zellweger Spectrum Disorder (ZSD)
Zellweger spectrum disorder (ZSD) is a rare, autosomal recessive peroxisomal biogenesis disorder with an estimated incidence of approximately 1 in 50,000 births, characterized by mutations in PEX genes that result in complete or partial loss of peroxisomal function. This leads to a severe multisystemic phenotype including profound neonatal hypotonia, craniofacial abnormalities, sensorineural hearing loss, vision impairment due to retinal dystrophy, hepatomegaly, and life-threatening neurological dysfunction such as seizures and progressive leukodystrophy.
Fig.1 Zellweger spectrum disorder (ZSD), rhizomelic chondrodysplasia punctata (RCDP) and reference (REF) individuals cluster by disease using CTDncd. (Thistlethwaite L R, et al., 2022)
Pathogenesis of Zellweger Spectrum Disorder (ZSD)
The pathogenesis of Zellweger spectrum disorder (ZSD) is exclusively caused by biallelic mutations in any of at least 13 different PEX genes, which encode peroxin proteins essential for peroxisome biogenesis. These mutations disrupt peroxisome assembly and import of matrix proteins, resulting in a global loss of peroxisomal metabolic functions. This includes the defective beta-oxidation of very long-chain fatty acids (VLCFAs) and branched-chain fatty acids, impaired synthesis of plasmalogens, and faulty bile acid metabolism, leading to the systemic accumulation of toxic metabolites and severe multisystemic pathology.
Therapeutic Development for Zellweger Spectrum Disorder (ZSD)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Cholic Acid | Restores primary bile acid synthesis to reduce production of toxic bile acid intermediates. | Bile acid synthesis pathway / Endogenous bile acid receptors | Approved |
| Bezafibrate | Activates PPAR receptors to enhance expression of fatty acid oxidation genes. | PPAR-α, PPAR-δ, PPAR-γ | Phase II |
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
To advance the effective management of Zellweger spectrum disorder (ZSD), Protheragen offers comprehensive diagnostic and therapeutic development services. With a focus on the diverse molecular mechanisms driving ZSD, we are dedicated to developing innovative and targeted therapies that address the significant unmet medical needs. Our team excels in creating highly accurate disease models, enabling rigorous evaluation of the safety, efficacy, and mechanism of action of potential therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Pex1-G844D Mouse Model: The model carries a common human patient mutation (c.2531G>A) and exhibits characteristic biochemical abnormalities, including plasmalogen deficiency and accumulation of very-long-chain fatty acids.
- Other Models
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Thistlethwaite L R, Li X, Burrage L C, et al. Clinical diagnosis of metabolic disorders using untargeted metabolomic profiling and disease-specific networks learned from profiling data[J]. Scientific reports, 2022, 12(1): 6556.