TPN-101 in Aicardi-Goutières Syndrome (AGS)

Inclusion Criteria

• •Patients must meet all of the following criteria:
• •Inclusion
• •1. Male or female participants of the following ages:
• •1. Cohort 1: Adults (≥ 18 years of age)
• •2. Cohort 2: Adolescents (12 to 17 years of age)
• •3. Cohort 3: Children 5 to 11 years of age
• •4. Cohort 4: Children 1 to \< 5 years of age and \>= 10 kg in weight
• •2. Molecular diagnosis of AGS due to biallelic mutations in 1 of the following 5 genes: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, or SAMHD1, or due to a recognized dominant mutation in TREX1
• •3. IFN score in peripheral blood \> 2 standard deviations above the mean score of healthy controls measured on 3 occasions, approximately 2 weeks apart, during the 6-week Screening Period.
• •4. Clinical syndrome consistent with AGS diagnosis based on clinical, CSF, and radiological findings. The following are examples of such findings (none of these are required for inclusion):
• •1. Early onset encephalopathy with psychomotor delay, spasticity, extrapyramidal signs, and microcephaly, the latter appearing in the first year of life
• •2. Calcifications particularly visible at basal ganglia level (putamen, pallidus, and thalamus), but also extending to the periventricular white matter
• •3. Cerebral white matter abnormalities
• •4. Cerebral atrophy
• •5. Important systemic symptoms in the early stages of the disease including irritability, feeding and sleeping difficulties, unexplained fevers, and the appearance of chilblain-like skin lesions on the fingers, toes, and ears
• •5. Has a reliable caregiver to accompany the patient to all study visits. Caregiver must have frequent contact with patient and be willing to monitor the patient's health and concomitant medications throughout the study