Wolfram Syndrome (WFS)
Wolfram syndrome (WFS), also known as DIDMOAD syndrome, is an inherited neurodegenerative disease with extremely high mortality. With advanced technology platforms and a team of professional research talents, our company can provide tailored solutions and extensive support for developing WFS diagnostics and therapies to accelerate your research process.
Introduction to WFS
WFS is a rare genetic disorder characterized by the destruction of pancreatic beta cells and atrophy of the optic nerve. WFS is associated with a range of other symptoms, including peripheral neuropathy, ataxia, cognitive impairment, renal tract abnormalities, gonadal atrophy, and mental disorders. The incidence of this disease ranges from 1/770 000 to 1/160 000.
Pathogenesis of WFS
WFS is an autosomal recessive disease caused by mutations in the WFS1 or CISD genes. The primary gene associated with WFS is WFS1. The WFS1 gene, located on chromosome 4p16.1, encodes the wolframin protein, which plays a crucial role in protein folding and endoplasmic reticulum (ER) homeostasis. Loss of function mutations in wolframin lead to the aggregation of misfolded proteins in the ER, triggering apoptosis and resulting in the characteristic features of WFS. In addition, studies have shown that the CISD gene is also associated with the occurrence of WFS. CISD encodes an ER intermembrane small protein (ERIS) that plays a role in Ca2+ homeostasis and mitochondrial function.
Fig.1 Structure of WFS1 gene. (Kõks, Sulev., 2023)Diagnostics Development of WFS
A combination of genetic testing and physical examination can accurately diagnose WFS.
Genetic testing plays a key role in confirming the diagnosis of WFS. WFS1 gene mutation detection can be performed using various methods, such as Sanger sequencing, targeted gene panels, or next-generation sequencing (NGS) technology. Identifying the pathogenic variant in the WFS1 gene can help establish a clear diagnosis and provide genetic counseling to affected individuals and their families.
Physical examination, such as optical coherence tomography (OCT) and magnetic resonance imaging (MRI), are valuable tools for assessing optic atrophy and monitoring disease progression. OCT provides detailed visualization of retinal structures, while MRI can reveal structural abnormalities in the brain and other affected organs, which supports the diagnosis of MFS.
Therapeutics Development of WFS
- Targets of WFS Therapy Development
| Target Name | Description |
|---|---|
| Endoplasmic Reticulum Stress Pathways | WFS is characterized by ER stress due to impaired calcium homeostasis and protein folding. Therapeutic approaches may involve targeting ER stress pathways to alleviate cellular stress and improve cell function. For example, studies have shown that ibudilast and a calpain inhibitor may be effective therapeutics for WFS by restoring calcium signaling and improving cell function. |
- Types of WFS Therapy Development
- Gene Therapy Development
Gene therapy holds promise for treating WFS by delivering functional copies of the mutated WFS1 gene to affected cells. For example, lentiviral gene therapy methods can successfully deliver the WFS1 gene and improve endoplasmic reticulum calcium homeostasis and neuronal survival.
- Stem Cell Therapy Development
The researchers induced pluripotent stem cells (iPSCs) in vivo from a mouse model of WFS and differentiated them into pancreatic beta cells. Impaired insulin secretion and increased sensitivity to endoplasmic reticulum stress were observed in these cells. This shows the potential of stem cell therapy in WFS intervention.
Our Services
Our company leads the way in rare disease research and the development of therapeutics. With a team of experienced scientists and researchers, we have established the advanced platforms dedicated to unraveling the complexities of rare diseases, including WFS.
Our research platforms
Our company is dedicated to offering diagnostic development services that facilitate early detection and precise diagnosis of WFS. Recognizing the significance of animal models in therapeutic drug development, we specialize in constructing WFS animal models using various species such as mice, rats, flies, zebrafish, and more. These models enable our customers to conduct drug safety evaluation and pharmacokinetics study on potential drug candidates.
Our services encompass a wide range of offerings beyond those mentioned, ensuring comprehensive support for WFS research and therapeutic development. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Kõks, Sulev. "Genomics of Wolfram Syndrome 1 (WFS1)." Biomolecules 13.9 (2023): 1346.
- Lee, Evan M., et al. "Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders." Frontiers in Genetics 14 (2023): 1198171.
- Morikawa, Shuntaro, et al. "Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments." Mammalian Genome (2024): 1-12.
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