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Aicardi-Goutières Syndrome (AGS)

The central challenge in caring for patients with Aicardi-Goutières syndrome (AGS) lies in dampening the damaging type I interferon response while sparing the host’s vital immune guards. Propelled by our pioneering insights into AGS, Protheragen is already advancing the next-generation therapies destined to reshape AGS management. Partnering with your team, we provide deep scientific knowledge and customized support at every stage.

Overview of Aicardi-Goutières Syndrome (AGS)

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder of the interferon pathway, defined by the early onset of encephalopathy, a gradual decline in neurological function, and signs of systemic inflammation. The syndrome was first documented in 1984 and, although it resembles congenital viral infection, it appears in the absence of any active virus. The condition instead stems from dysregulated nucleic acid sensing and type I interferon signaling. AGS is estimated to occur in about 1 to 2 cases for every 100,000 live births.

Fig.1 Mutations in Aicardi-Goutières syndrome (AGS)-related genesresult in overproduction of type I interferons and cause AGS. (Liu A, Ying S., 2023)

Pathogenesis of Aicardi-Goutières Syndrome (AGS)

Aicardi-Goutières syndrome (AGS) results from genetic changes that disrupt nucleic acid metabolism, primarily within a defined set of genes: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR1. These defects cause excessive intracellular self-DNA and self-RNA, which provoke a sustained type I interferon (IFN-α/β) response. This response is mediated by cytosolic sensors such as cGAS-STING and MDA5/RIG-I, culminating in persistent neuroinflammation, calcification of the cerebral white matter, and the progressive deterioration of neurological function that defines the phenotype.

Fig.2 Numbers and percentages of patients with Aicardi-Goutièressyndrome (AGS) with or without mutations in TREX1, RNASEH2A, RNASEH2B,RNASEH2C, SAMHD1, ADAR1 and IFIH1 genes. (Garau J, et al., 2019)

Therapeutic Development for Aicardi-Goutières Syndrome (AGS)

Drug Names	Mechanism of Action	Targets	NCT Number	Research Phase
TPN-101	Nucleoside reverse transcriptase inhibitor that blocks retrotransposition of endogenous nucleic acids	Reverse transcriptase (RT) of endogenous retroelements	NCT05613868	Phase IIa
Baricitinib	JAK1/2 inhibitor that suppresses downstream signaling of type I interferons (IFN-α/β)	JAK1/JAK2 kinases	NCT06898372	Phase III

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

Specializing in comprehensive solutions for Aicardi-Goutières syndrome (AGS), Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits for early disease identification. Our therapeutic development pipeline leverages exclusive disease models, such as physiologically representative blood-brain barrier (BBB) models, to expedite the exploration and authentication of central nervous system (CNS) targeted treatments.

Therapeutic Development Services

By Molecule Types

By Mechanism of Action

Disease Model Development Services

Model Types	Model Names
In Vitro Models	Patient-Derived Cell Model Neuronal Cell Model Glial Cell Model	Co-Culture Model Brain Organoid Spinal Cord Organoid
Microfluidic Models	Neurovascular Unit (NVU) Model Axon Degeneration Model Neuromuscular Junction (NMJ) Model	Neuroinflammation Model Synaptic Plasticity Model Organoid-on-a-Chip Model
Animal Models	Trex1^–/– Mice: Mice lacking the TREX1 gene accumulate cytosolic DNA, leading to chronic activation of the type I interferon response, mimicking key features of AGS. ADAR1-deficient Mice: Loss of ADAR1, an RNA-editing enzyme, results in aberrant immune activation due to unedited endogenous RNA, contributing to AGS-like autoinflammatory and neurodevelopmental phenotypes. RNase H2-deficient Mice: Mice with mutations in RNase H2 genes accumulate ribonucleotides in DNA, triggering DNA damage responses and type I interferon signaling, modeling AGS pathology.

To advance the commercialization of novel therapies for Aicardi-Goutières syndrome (AGS), Protheragen provides comprehensive preclinical research services, covering pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

Liu A, Ying S. Aicardi–Goutières syndrome: A monogenic type I interferonopathy[J]. Scandinavian Journal of Immunology, 2023, 98(4): e13314.
Garau J, Cavallera V, Valente M, et al. Molecular genetics and interferon signature in the Italian Aicardi Goutières syndrome cohort: report of 12 new cases and literature review[J]. Journal of Clinical Medicine, 2019, 8(5): 750.

For research use only. Not intended for any clinical use.