Stargardt Disease (STGD)
Stargardt disease is a genetic eye disorder that leads to retinal degeneration and vision loss, representing the most prevalent type of inherited macular degeneration. The gradual loss of vision in Stargardt disease results from the degeneration of photoreceptor cells in the macula, the central part of the retina. Our company is fully equipped to support your drug and therapy development requirements for treating Stargardt Disease.
Overview of Stargardt Disease
Stargardt disease, the most common form of inherited macular degeneration, affects approximately 1 in 8,000 to 10,000 people. It typically presents in childhood or adolescence and leads to progressive vision loss due to mutations in the ABCA4 gene, which causes toxic lipid byproducts to accumulate in the retina. Recent research has focused on developing therapies to slow disease progression.
Fig. 1 The ABCA4 exon map, showing the reading frame and the functional protein domains encoded by the corresponding exons. (Huang, D., et al., 2022)Pathogenesis of Stargardt Disease
The pathogenesis of Stargardt disease primarily involves mutations in the ABCA4 gene, which is responsible for the transport of retinoids in photoreceptor cells. These mutations impair the function of the ABCA4 protein, leading to the failure in the transport of N-retinylidene-phosphatidylethanolamine (N-ret-PE) across the disc membrane. This failure results in the accumulation of toxic bis-retinoids like A2E in the retinal pigment epithelium (RPE), causing RPE dysfunction and cell death. Consequently, this leads to the progressive degeneration of photoreceptor cells and vision loss.
Fig. 1 schematic showing the retinoid cycle. (Huang, D., et al., 2022)New Diagnostic Approaches of Stargardt Disease
- Genetic Sequencing: The primary method for diagnosing Stargardt disease is through genetic testing, focusing on mutations in the ABCA4 gene. Whole exome sequencing (WES) has emerged as a robust tool for identifying these mutations.
- Next-Generation Sequencing (NGS): NGS technologies have enhanced the accuracy and scope of genetic testing for inherited retinal diseases, including Stargardt disease. NGS allows for the simultaneous analysis of multiple genes, making it possible to identify both common and rare mutations associated with the disease
Therapeutics Development of Stargardt Disease
Small molecule drugs aim to modulate biochemical pathways involved in Stargardt disease to slow down or prevent the accumulation of toxic lipofuscin in the retina. Emixustat Hydrochloride is designed to inhibit RPE65, an enzyme involved in the visual cycle. By inhibiting RPE65, emixustat reduces the formation of toxic retinal byproducts.
Gene therapies aim to correct the underlying genetic defect in Stargardt disease by delivering functional copies of the ABCA4 gene or modulating gene expression. Adeno-associated virus (AAV) vectors are commonly used to deliver the correct version of the ABCA4 gene to retinal cells. Early results showing potential improvements in retinal structure and function.
Cell therapies aim to replace or repair the damaged retinal cells in Stargardt disease, particularly the RPE and photoreceptors. One promising approach involves the transplantation of RPE cells derived from human embryonic stem cells. These cells replace the dysfunctional RPE cells in Stargardt disease individuals.
Monoclonal antibodies are designed to target specific proteins or pathways involved in the disease process. Anti-Lipofuscin antibodies could bind to the toxic components of lipofuscin, facilitating their removal and potentially slowing the progression of Stargardt disease.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Stargardt Disease therapy strategies and ensure robust support throughout the process.
Platforms of Stargardt Disease Therapy Development
Animal Models of Stargardt Disease
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to Stargardt Disease. These models allow researchers to simulate and study the complex biological processes associated with Stargardt Disease. | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Stargardt Disease. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
Beyond these models, our extensive services also include additional models that focus on specific signaling pathways and molecular targets.
Should our services match your objectives, please contact us for more details.
References
- Huang, D., et al., "Stargardt disease and progress in therapeutic strategies." Ophthalmic Genet, (2022). 43(1): p. 1-26.
- Piotter, E., et al., "Therapy Approaches for Stargardt Disease." Biomolecules, (2021). 11(8).
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.