Aicardi-Goutieres Syndrome (AGS)
Aicardi-Goutieres syndrome (AGS) is classified as a multi-system autoimmune syndrome that has an aggravated form of Type I interferon signaling pathway. In order to facilitate research aspects of AGS, specialized drug and therapy development services are crucial. We are capable of fulfilling your drug and therapy development specific needs for AGS therapy.
Introduction to Aicardi-Goutieres Syndrome
Aicardi-Goutieres syndrome is a milder form of AGS and is characteristic of microcephaly, cerebral calcifications and lymphocytic pleocytosis in CSF. The disorder is associated with abnormal inflammation systemic alpha interferon production. The individual develops severe neurological deficits as a result of inflammation, which is autoimmune in nature, during the first year of life. Researchers have been able to trace genetic alterations responsible for AGS. Among people in Denmark, it is estimated that the incidence rate is around 0.0539 per 100,000 people aged 0 to 18 every year.
Fig. 1 Schematic of the human ADAR1 gene. (Rice, G.I., et al., 2012)Pathogenesis of Aicardi-Goutieres Syndrome
- Aicardi-Goutieres Syndrome has been linked to TREX1, ADAR1, RNASEH2, and SAMHD1 genes, all of which modify the Interferon metabolism responsible for nucleic acid metabolism that is disrupted.
- This cGAS-STING type of mutation constantly triggers the production of type 1 interferons by pattern recognition receptors.
- Interferon inflammation response causes tissues to be damaged and for chronic inflammation to occur. This phenomenon is well known and represents the challenges Interferon pertinent elevated or increased interferon levels serves as primary diagnostic marker. It does for the diseases most severe neurological, dermatological manifestations.
Fig. 2 Proposed model of immune system stimulation by nucleic acids accumulating as a consequence of Aicardi–Goutières syndrome (AGS)-related protein dysfunction. (Crow, Y.J., et al., 2014)Diagnosis Development of Aicardi-Goutieres Syndrome
There has been a recent focus on identifying AGS based on its biomarkers, specifically those affiliated with the activated of the interferon (IFN) pathway induced by AGS traits. Some researchers are looking into the activation of blood interferon stimulated genes (ISGs) and interferon signatures as possible biomarkers for AGS because of their promise in enhancing the accuracy and speed of AGS diagnosis. Individuals with AGS persistently elevated IFN-alpha levels in their cerebrospinal fluid (CSF) and serum.
Therapy Development of Aicardi-Goutieres Syndrome
Interferon pathway small molecules have proven useful in the management of AGS. One such molecule is Baricitinib. Being an Inhibitor of Janus Kinase (JAK), Baricitinib prevents receptors and other molecular mediators of Type i Interferon from being utilized. Baricitinib could possibly attack the heightened immunity of AGS individuals.
Enhanced immune suppression or repair of the immune system dysfunction represent the early stages of exploration of cell therapies for AGS. One attempt in this regard is the use of regulatory T cells (Tregs), which may suppress autoimmune aspects of AGS. Another approach which may be utilized is mesenchymal stem cell (MSC) therapy.
The application of monoclonal antibodies, which target the immune system's interferon as in the case of sifalimumab, is being explored in its relation to AGS therapy. Sifalimumab's effectiveness relies on its ability to neutralize IFN-α. Reducing the overexpression of interferon-stimulated genes in AGS should be possible by the usage of compounded antibodies targeted to AGS.
At this point, AGS gene therapies tend to remain within sci-fi films and novels. They could provide a way to correct the genetic defects that the syndrome has, though things like genome editing using gene editing technique is one that can hope to fix single mutations in genes like a 'corrective action system', at some point in the near future.
Our Services
We develop personalized AGS therapy solutions with direct input from our partners so as to provide the best drug and unmatched assistance for the therapeutic process.
Platforms of Aicardi-Goutieres Syndrome Therapy Development
Animal Models of Aicardi-Goutieres Syndrome
We possess unique know-how in the development and application of appropriate animal models of any disease that closely reproduce the pathology and therapeutic response that make it possible to test the prospective therapies for safety and effectiveness.
| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human AGS. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Rice, G.I., et al., "Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature." Nat Genet, (2012). 44(11): p. 1243-1248.
- Crow, Y.J., et al., "Therapies in Aicardi-Goutieres syndrome." Clin Exp Immunol, (2014). 175(1): p. 1-8.
- Liu, A. and Ying, S., "Aicardi-Goutieres syndrome: A monogenic type I interferonopathy." Scand J Immunol, (2023). 98(4): p. e13314.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.