# Clinical measures in Aicardi Goutieres Syndrome

> **NIH NIH K23** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $184,977

## Abstract

Aicardi Goutières Syndrome (AGS) is a leukodystrophy characterized by early neurologic disability.
While genetically heterogeneous, all genotypes activate a common pathway: interferon (IFN) production
leading to Janus kinase (JAK) activation and transcription of IFN-stimulated genes (ISG). My preliminary work
supports that there are two distinct phenotypes of AGS: a severe form characterized by global impairment and
a milder form characterized by spastic paraparesis with preserved cognition. In our leukodystrophy center, we
follow more than 100 children with AGS, two-thirds of whom are affected by the severe form. Despite a general
understanding of AGS and growing interest in therapy development, progress has been limited by the lack of
appropriate assessment tools.
 Because of sustained IFN expression, we hypothesized that children with AGS may respond to anti-
inflammatory medications. In 2016, we launched a therapeutic program using baricitinib, a JAK inhibitor. Our
preliminary results suggest that baricitinib decreases IFN-stimulated gene expression (ISG score by standard
mRNA assay) and improves symptoms such as irritability and skin inflammation as reported by a symptom
diary. While most families report neurologic improvement, preliminary results from traditional outcome
measures are inconclusive. As supported by our equivocal findings, there is a critical, unmet need for (1) the
ability to predict neurologic trajectory and therapeutic responsiveness at disease onset, (2) a novel, disease-
specific outcome measure that is sensitive to neurologic change and clinically relevant to this unique
population, and (3) the characterization ISG scores as an AGS biomarker. Our parallel treated and untreated
cohorts will allow me to establish the value of these novel measures in defining both the neurologic trajectory
and potential therapeutic response to baricitinib.
 The anticipated outcome of this proposal will be (1) a panel of features capable of predicting neurologic
trajectory prior to therapeutic intervention, (2) a novel disease-specific assessment measure, and (3) a defined
role of ISGs as a biomarker in AGS. These advances will be invaluable for future cohort selection and the
evaluation of efficacy in future clinical trials benefitting AGS. With this final phase of intensive mentored
training, I will be poised for success with future R01 applications related to the design of rare-disease outcome
measures for children affected by leukodystrophies.!

## Key facts

- **NIH application ID:** 10023201
- **Project number:** 5K23NS114113-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Laura Ann Adang
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,977
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023201

## Citation

> US National Institutes of Health, RePORTER application 10023201, Clinical measures in Aicardi Goutieres Syndrome (5K23NS114113-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10023201. Licensed CC0.

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