Neuropediatrics 2017; 48(S 01): S1-S45
DOI: 10.1055/s-0037-1602921
OP – Oral Presentations
Georg Thieme Verlag KG Stuttgart · New York

The Enemy Within: Deleterious Consequences of an Inappropriate Antiviral Response for the Central Nervous System

T. Deba
1  Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Bereich Neuropädiatrie, Deutschland, Münster, Germany
,
J. Althaus
1  Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Bereich Neuropädiatrie, Deutschland, Münster, Germany
,
B. Fiedler
1  Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Bereich Neuropädiatrie, Deutschland, Münster, Germany
,
C. Groß
2  Universitätsklinikum Münster, Klinik für Allgemeine Neurologie, Bereich Liquordiagnostik bei Neurologischen Erkrankungen, Deutschland, Münster, Germany
,
C. Hinze
3  Universitätsklinikum Münster, Klinik für Pädiatrische Rheumatologie & Immunologie, Deutschland, Münster, Germany
,
R. Sträter
4  Universitätsklinikum Münster, Klinik für Pädiatrische Hämatologie & Onkologie, Deutschland, Münster, Germany
,
M. A. Lee-Kirsch
5  Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Klinik für Kinder- und Jugendmedizin, Molekulare Pädiatrie, Deutschland
,
H. Omran
1  Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Bereich Neuropädiatrie, Deutschland, Münster, Germany
,
G. Kurlemann
1  Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Bereich Neuropädiatrie, Deutschland, Münster, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2017 (online)

 

Background/Purpose: Aicardi-Goutierès syndrome (AGS) is a heterogenous congenital inflammatory disease predominantly affecting the central nervous system mimicking a chronic viral infection. AGS so far has proven refractory to various treatment approaches. In AGS, intracellular nucleic acid accumulation is a key trigger for type I interferon release, similar to that seen in antiviral immunity. Retroelements potentially are a major source of pathogenic nucleic acids; thus, reverse transcriptase inhibitors (RTI) are being evaluated in clinical trials in AGS (https://clinicaltrials.gov/show/NCT02363452).

Methods: We treated three AGS patients with a combination of RTIs on an individual curative trial basis.

Results: Two patients with RNASEH2B mutation and one with SAMHD1 mutation have received RTI treatment for more than 2 years. Clinically, improvement regarding irritability was noted; CSF cell count and protein, neopterin levels, soluble CD25 levels, and IFN α activity improved or normalized. In one patient, symptoms are controlled to a large extent; however, a cerebral vasculitis and glaucoma progressed on continuous treatment. In another case, parental incompliance illustrated the efficacy of antiretroviral therapy. Inconclusive results on repeated interferon signature analyses were a common feature in all our cases.

Conclusion: The rapidly growing understanding of the disease pathomechanisms in AGS may lead to improved treatment strategies. Our preliminary data demonstrate that blocking transcription of endogenous retroelements via RTIs may be a useful tool in the treatment of AGS. However, judging treatment efficacy is extraordinarily challenging in AGS due to the difficulty to separate disease activity from therapeutic effects. Therefore, controlled studies are needed to better define potentially efficacious treatments.