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Aicardi-Goutières Syndrome (AGS)

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

Overviewof Aicardi-Goutières Syndrome (AGS)

Aicardi-Goutières syndrome (AGS) is a rare geneticdisorder of the interferon pathway, defined by the early onset ofencephalopathy, a gradual decline in neurological function, and signs ofsystemic inflammation. The syndrome was first documented in 1984 and, althoughit resembles congenital viral infection, it appears in the absence of anyactive virus. The condition instead stems from dysregulated nucleic acidsensing and type I interferon signaling. AGS is estimated to occur in about 1to 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)

Pathogenesisof Aicardi-Goutières Syndrome (AGS)

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

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)

TherapeuticDevelopment for Aicardi-Goutières Syndrome (AGS)

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

Disclaimer:Protheragen focuses on providing preclinical research services. This table isfor information exchange purposes only. This table is not a treatment planrecommendation. For guidance on treatment options, please visit a regularhospital.

Our Services

Specializing in comprehensive solutions forAicardi-Goutières syndrome (AGS), Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits forearly 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, mimickingkey features of AGS. ADAR1-deficient Mice: Lossof ADAR1, an RNA-editing enzyme, results in aberrant immune activation due tounedited endogenous RNA, contributing to AGS-like autoinflammatory andneurodevelopmental phenotypes. RNaseH2-deficient Mice: Micewith mutations in RNase H2 genes accumulate ribonucleotides in DNA,triggering DNA damage responses and type I interferon signaling, modeling AGSpathology.

To advance the commercialization of novel therapies for Aicardi-Goutièressyndrome (AGS), Protheragen provides comprehensive preclinical research services, coveringpharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you areinterested in our services, please feel free to contact usfor more detailsand quotation information of related services.

References

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

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