Hurler Syndrome
The main challenge in treating Hurler syndrome is finding ways to formulate therapies which augment cognitive functioning and simultaneously control progressive somatic complications in the disease's later stages. At Protheragen, we are focused on improving the treatment of Hurler syndrome with the application of new technologies in therapeutic development alongside disease modeling services. We aim to offer comprehensive solutions for the entire workflow of therapeutic development.
Introduction to Hurler Syndrome
Hurler syndrome (mucopolysaccharidosis type I, MPS I) is a critical form of a lysosomal storage disorder associated with a malfunction of the enzyme α-L-iduronidase, responsible for the breaking down of glycosaminoglycans (GAGs). The enzyme's malfunction causes the accumulation of heparin and dermatan sulfate in lysosomes which leads to progressive multisystemic illness. This illness could affect multiple body system including the nervous system, skeletal system, eyes, and heart.
Fig.1 The pathogenetic cascade of mucopolysaccharidoses (MPSs). (Fecarotta S, et al., 2020)
Pathogenesis of Hurler Syndrome
Hurler syndrome occurs due to the lack of the lysosomal enzyme α-L-iduronidase because of changes in the IDUA gene, which leads to the progressive buildup of glycosaminoglycans (GAGs), especially heparan and dermatan sulfate, in various tissues and organs. This form of lysosomal storage causes cellular damage, which leads to, among other things, neurodegeneration, skeletal deformities, and cardiopulmonary complications.
Fig.2 Representative inflammatory pathways and activated innate immunity in mucopolysaccharidosis (MPS). (Ago Y, et al., 2024)
Therapeutic Development for Hurler Syndrome
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| SB-318 | AAV5 vector delivering functional IDUA gene to restore α-L-iduronidase production | IDUA gene | NCT02702115 | Phase I/II |
| OTL-203 | In vitro lentiviral gene therapy; autologous hematopoietic stem cells (HSCs) are genetically modified to express functional α-L-iduronidase (IDUA), which complements the defects of Hurler syndrome. | IDUA gene | NCT06149403 | Phase I/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
At Protheragen, we focus on preclinical research in Hurler syndrome, providing comprehensive solutions from biomarker identification to development of CNS targeted therapeutics. Our expertise covers disease modeling, including patient-derived iPSCs, genetically engineered models, and advanced blood-brain barrier (BBB) models for evaluating drug penetration and neuroprotective efficacy. We provide partners with target validation, lead compound optimization, and comprehensive preclinical research services.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
| In Vitro Model Development | |
| Microfluidic Model Development | |
| Animal Model Development | |
|
|
At Protheragen, we are committed to validating and optimizing therapies for Hurler syndrome through comprehensive pharmacodynamics (PD), pharmacokinetics (PK) and toxicology research services to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Fecarotta S, Tarallo A, Damiano C, et al. Pathogenesis of mucopolysaccharidoses, an update[J]. International Journal of Molecular Sciences, 2020, 21(7): 2515.
- Ago Y, Rintz E, Musini K S, et al. Molecular mechanisms in pathophysiology of mucopolysaccharidosis and prospects for innovative therapy[J]. International Journal of Molecular Sciences, 2024, 25(2): 1113.