Mowat-Wilson Syndrome (MWS)
Mowat-Wilson syndrome (MWS) is an incredibly rare disorder which poses a great challenge in developing effective therapeutic measures owing to the extensive and complex genetic factors. With our proven record in developing therapies for MWS, Protheragen is uniquely positioned to offer customized assistance and full spectrum guidance to help you navigate from MWS therapy discovery to therapy development and commercialization.
Introduction to Mowat-Wilson Syndrome (MWS)
Mowat-Wilson syndrome (MWS) is an uncommon disorder that affects multiple systems in the body and has a neurodevelopmental component. It is caused by haploinsufficiency of the ZEB2 gene on chromosome 2q22.3. MWS was first described in 1998. Its hallmark features include specific craniofacial abnormalities, an intellectual disability, Hirschsprung disease, and several heart and other organ congenital anomalies. The estimated prevalence of MWS is 1 in 50,000-100,000 live births. However, the true incidence is likely higher due to the condition being underdiagnosed with a variable phenotype.
Fig.1 Structure of the ZEB2 gene. (Zhoulideh Y, Joolideh J., 2024)
Pathogenesis of Mowat-Wilson Syndrome (MWS)
Mowat-Wilson syndrome (MWS) occurs as a result of heterozygous loss-of-function mutations or deletions on the ZEB2 gene, which encodes a SMAD-interacting transcriptional repressor critical for the development of neural crest cells. ZEB2 haploinsufficiency disrupts the formation of the enteric nervous system, as well as craniofacial and central nervous system morphogenesis. Impaired TGF-β/SMAD signaling alongside blocked epithelial transformation give rise to numerous and diverse system malfunctions characteristic of the syndrome.
Fig.2 TGF-β/SMAD signaling pathway for regulating the expression of target genes. (Zhoulideh Y, Joolideh J., 2024)
Therapeutic Development for Mowat-Wilson Syndrome (MWS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Valproic acid | Valproic Acid is an anticonvulsant and mood-stabilizer that increases the availability of gamma-aminobutyric acid (GABA) and affects ion channels and histone deacetylases. | GABA receptors, ion channels, histone deacetylases | Approved |
| Risperidone | Risperidone is an atypical antipsychotic that works by antagonizing dopamine D2 and serotonin 5-HT2A receptors, helping to adjust imbalances in brain neurotransmitters. | Dopamine D2 receptors, serotonin 5-HT2A receptors | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. 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
As a professional preclinical research service provider, Protheragen is dedicated to accelerating breakthroughs in the field of Mowat-Wilson syndrome (MWS). We offer end-to-end solutions encompassing diagnostic development, novel therapeutic development, precise disease modeling, and rigorous preclinical validation. Our blood-brain barrier model enables critical assessments of drug permeability in the central nervous system (CNS), ensuring optimal brain exposure while minimizing systemic toxicity, thus expediting the development of effective therapies.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- Zeb2 Conditional Knockout Model: Our scientists use genetic engineering techniques to knock out the Zeb2 gene in mouse neural crest cells or GABAergic interneurons to construct the model.
- Other Models
Specializing in comprehensive preclinical assessment, Protheragen offers professional pharmacodynamic (PD), pharmacokinetic (PK) and toxicology research services to accelerate the therapeutic development of Mowat-Wilson syndrome (MWS).If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Zhoulideh Y, Joolideh J. Mowat-Wilson syndrome: unraveling the complexities of diagnosis, treatment, and symptom management[J]. Egyptian Journal of Medical Human Genetics, 2024, 25(1): 40.