Applications Submitted for Multiple Patient-Partnered Collaborations (PPC) Grants

This week, the AGSAA quietly submitted applications with separate teams of researches for two Chan Zuckerberg Initiative (CZI) grants.

• Patient-Partnered Collaborations for Single-Cell Analysis of Rare Inflammatory Pediatric Disease

• Patient-Partnered Collaborations for Rare Neurodegenerative Disease

Each of these competitive grants would provide $2 million dollars over four years for projects aimed at better understanding the direct mechanics of AGS and establishing the foundations for novel treatment strategies. Almost a quarter of each award would be paid to the AGSAA directly, to fund our research coordination, community education, development of a biorepository, and direct involvement in the science. The AGSAA’s deep engagement in these projects represents a fairly novel approach to this type of work, one that affords rare disease communities more opportunities to promote collaboration and continuity of work in their disorders. As such, the AGSAA has named Patrick Winters as Co-PI on both projects, to serve on equal standing with the clinical and lab principal investigators. The total immersion in these projects will train our organization to be a more effective research accelerator!

We’d like to share a bit about how these collaborations came about because our community and supporters played a large role. On Rare Disease Day, our families, friends, and followers raised money to fund a small grant for an early career researcher. With the cash in hand, we surveyed our network of scientists to find labs and individuals in a position to make good use of the opportunity. In doing so, we connected with a number of new PIs and learned a great deal more from our friends about ongoing work and potential opportunities. Not only were we able to attract interest in our grant, we found scientists invigorated by eagerness and the opportunity to meaningfully connect their work to the AGS community. We even held a small “get to know each other” meeting between a handful of families and a laboratory that had never spoken with or met a person with AGS. Involving and embedding ourselves with the science strengthens the relevancy of the work being done and our potential to improve it. And, it all sprung from our community’s ever increasing engagement and teamwork.

COVID-19 Vaccine Guidance

NOTE: This manuscript was accepted and published in Molecular Genetics and Metabolism on October 10th. See SARS-CoV-2 mRNA-based vaccines in the Aicardi Goutières Syndrome.

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Yesterday, our clinical collaborators at the Children’s Hospital of Philadelphia uploaded a pre-print of an article we contributed to about COVID-19 vaccines and their safety within AGS. Please note that pre-prints have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive. However, the conclusions of the authors remain; and we wanted to get this to our community as quickly as possible.

Based on experiments using blood samples from AGS patients, the authors have determined that the currently approved COVID-19 vaccines should not stimulate AGS disease activity more than other vaccine technologies. They’ve included our findings from our patient registry that suggest COVID-19 vaccination is safer than the risk involved with a live infection.

In the context of continued COVID-19 infections in the community, however, we are cautiously recommending that AGS affected individuals consider being vaccinated with one of the United States Food and Drug Administration approved mRNA vaccines, as applicable for their ages in the general population, unless individuals have documented vaccine related adverse events.

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mRNA-based vaccines against SARS-CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutières Syndrome.

Asako Takanohashi, Mohamad-Gabriel Alameh, Sarah Woidill, Julia Hacker, Benjamin Davis, Guy Helman, Francesco Gavazzi, Laura Adang, Russell D'Aiello, Patrick Winters, Devon Cordova, Taibeen Khandaker, Houping Ni, Ying Tam, Paulo Lin, Drew Weissman, Justine Shults, Adeline Vanderver

bioRxiv 2022.05.18.492546; doi: https://doi.org/10.1101/2022.05.18.492546

Join Our Growing Team

Our Team is Growing!

Welcome and Cheer Our New Members Who Will shape the future of Aicardi-Goutieres Syndrome and the AGSAA

2022 has been a landmark year for the AGSAA. We’ve rapidly expanded our team, increased our efforts, and grown a collaborative network of clinicians, researchers, and industry groups. Still, nothing has a more profound impact on a small organization than committed volunteers. As we identify opportunities and needs (e.g. a biorepository, newborn screening, clinical network, local support teams, etc.) we rely on volunteers to lend a hand.

Claire Martinez has been quietly serving as unofficial outreach coordinator for a couple of months. If you’ve been newly diagnosed, you have probably heard from her. She has joined the AGSAA to provide direct support and information to families as they navigate this rare and sometimes upside down life with AGS. Claire will be leading and developing our international AGS Champions program to train and empower global volunteers to provide local support.

Ashley Matura has joined as AGSAA accountant, but she’s passionate about other things like beer and advocacy. She is a CPA with public accounting experience and 10 years in industry. Very recently, she has volunteered to head the development of our newborn screening (NBS) program, drawing on her advocacy experience with NBS for cytomegalovirus.

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The AGSAA still has many unmet needs and roles that span multiple concerns: basic organizational development and governance, family support and assistance, research development, marketing and fundraising, etc. If you’re interested in volunteering or learning more about what you can do, contact us! info@agsaa.org

Additional Support and Resources for Securing Treatment with JAK Inhibitors

While many AGS families have successfully advocated for treatment with JAK inhibitors, there still remain significant hurdles to overcome. In a recent conversation with Dr. Laura Adang of the Children’s Hospital of Philadelphia, the AGSAA learned that the process of acquiring health insurance approval in the US for barcitinib is more fraught than we had realized. We believe that many families suffer the stress of this silently, relying on their doctors to accumulate sufficient evidence and make the appropriate appeals. We wholeheartedly recommend that families involve themselves in this process by providing their doctors with information we’ve compiled and submitting letters of appeal using a template developed by community members. Additionally, the AGSAA has been quietly developing a network of doctors and contacts in and outside of the United States, precursors to what we are calling our volunteer champions and clinical network. We’ll be your partners, if requested, advocating on your behalf. Contact support@agsaa.org, if needed, and please review our information, references, and resources for advocating for treatment.

Register As an Organ Donor, Help Cure AGS

Last evening we held an informal meeting to introduce Drs. Adeline Vanderver and Markus Hofer. Both have worked extensively to characterize and understand the mechanisms that lead to brain damage in Aicardi-Goutieres Syndrome. Efforts to model AGS in mice and artificial organoids have proven difficult, and questions remain about the particular cell types, tissues, and pathways primarily responsible for AGS. In order to confirm observations about disease mechanisms observed in model organisms, Dr. Markus Hofer has extensively studied brain tissue donated by AGS families worldwide. However, the age and limited availability of these tissues present challenges to this work. The number of AGS brains available for research can be counted on two hands, and the legacy methods used to preserve them (e.g. in formaline/formaldehyde) make it challenging to extract RNA for modern genetic studies. Additionally, many of the brains were donated before the identification of AGS genes and the prevalence of modern genetic testing. We cannot confidently associate clinical information and confirm genotype with donated tissues. Indeed, much of our conversation focused on attempts to identify the specific doctors and patients related to the tissues being examined.

Admittedly, organ donation is not something we as parents want to consider. I would rather avoid the thought of making decisions surrounding the loss of my child, but we can resolve now to improve the lives of those with AGS ahead of us. We can accelerate research by donating to this invaluable and precious resource. Register to donate today.

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NIH NeuroBio Bank

The National Institute of Health (NIH) in the United States maintains the NIH NeuroBio Bank, a biobank of brains donated for scientific research. This precious and limited resource allows researchers to examine and analyze AGS in humans, a critical piece of solving the complexity of AGS. Consider registering today to help the AGS community.

Studies using donated brain tissue following death are the most promising avenue for researchers to learn how to prevent and cure disorders of the brain.

Patient Registry Breakdown, May 2022

Are you represented in the AGS patient registry? If you’re outside of the United States, chances are that you’re not. We encourage everyone to participate, but we recognize that the language barrier may make it difficult. Our registry software has translation limitations that we will continue to work on. Still, we have lots of missing data for those of you that have participated. Please try to complete all of the surveys so that we can better characterize the community. We’ve begun writing a survey to explore triggers and flares, and we will need much of this basic demographic data complete to interpret the results.

We have 112 members that have created accounts and joined our AGSAA Community in Luna. Of that group, 41 have joined our registry study and completed at least one survey. By far, we have had the highest engagement in our COVID-19 investigations. We’ve submitted data and experiences from our registry to publish alongside lab experiments done by the Children’s Hospital of Philadelphia to investigate the safety of COVID-19 vaccination in AGS. We’ll share as soon as it’s published or we have an open pre-print available!

About half of our active participants still have some basic surveys to complete, so we lack data about their country of residence, age group, genotype, and medication/therapy status. We request that everyone get these out of the way because they allow us to characterize participants and take a deeper look at how certain details affect their experiences (e.g. whether genotype affects safety of COVID-19 vaccination). Nonetheless, we have participants in multiple countries, all age groups, and with most AGS genotypes.

We’ve also computed scores for participants using the AGS Scale (doi: 10.1016/j.ymgme.2022.03.010). This quick survey developed by the Children’s Hospital of Philadelphia characterizes the neurological severity of AGS in individuals. So far, we see that our registry represents the spectrum of AGS pretty well. We want to avoid bias in our registry and insights, so please help us by completing this survey to ensure that we consider everyone!