Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome

The investigators propose that a trial to assess the proof of principle that antiretroviral
therapy through a drug combination of Tenofovir (TDF) and Emtricitabine (FTC) can decrease
endogenous retroelement accumulation, and alter interferon signaling in Aicardi Goutieres
Syndrome (AGS) patients is reasonable and warranted at this time, based on existing in vitro
and animal data. Additionally, this trial will further the investigators understanding of
this disorder, measuring for the first time retroelements in human participants, exploring
the retroviral burden in cerebrospinal fluid (CSF), the Interferon (IFN) signaling response,
as well as evaluating antigen targets of autoimmunity and cytokines. If successful, this
approach will clearly demonstrate the need for a larger trial of antiretrovirals in AGS with
more clinically relevant outcomes.

Inclusion Criteria:

- Molecular, neuroimaging, and clinical findings consistent with a diagnosis of AGS,
with the exception of Double-stranded RNA-specific adenosine deaminase (ADAR1) and
IFIH1, which are not postulated to result in nucleic acid accumulation

- Evidence of interferon activation such as elevation of CSF
neopterin/tetrahydrobiopterin measured on the first evaluation.

- Ages 2-18 years (the age of 2 years is used because the drugs are FDA approved in
children greater than 2 years)

- Weight of at least 10 kg

- Willingness to undergo serial lumbar punctures and blow draws for evaluation of
laboratory based outcome measures

- Willingness to abstain from initiating the use of immune modulating therapies
including corticosteroids

- Able to receive medications orally, by nasogastric (NG) tube or by Gastric (G)-tube

- No concomitant illness which would preclude safe participation as judged by the
investigator

- Signed informed consent by the subject's legally acceptable representative

- Negative testing for HIV

- Negative testing for Hepatitis B

- Concurrent enrollment in the Myelin Disorders Biorepository Project (MDBP,
ClinicalTrials.gov NCT03047369) and willingness to undergo associated procedures

Exclusion Criteria:

- Age < 2 years or >18 years

- Hepatic insufficiency with liver function tests greater than 3-times the upper limit
of normal

- Renal insufficiency with creatinine clearance <60

- Significant malabsorption

- Any clinical or laboratory abnormality or medical condition that, at the discretion of
the investigator, may put the subject at an additional risk by participating in this
study

- HIV infection

- Hepatitis B infection

- Mutations in ADAR1 or IFIH1