An Open Letter to AGS Physicians

PO Box 2821 
Crested Butte, CO 81224 
+1 917 960 8733
https://agsaa.org/
info@agsaa.org

Esteemed Provider,

The Aicardi Goutieres Syndrome Advocacy Association (AGSAA) would like to ensure that you’re aware of recent developments in the treatment of Aicardi-Goutieres Syndrome (AGS). We understand that familiarity with our rare disorder comes at a premium, and it’s likely that you will benefit from resources and references we can provide to improve the care of your patient. Most importantly, we’ve accumulated an explanation, testimonials, and references to aid parents and physicians in treating AGS with JAK inhibitors. Many children and adults affected by AGS have had their disease managed effectively by treatment with baricitinib, ruxolitinib or (to a lesser extent) tofacitinib, all of which are immune modulating agents. These medicines are approved in most countries and have been used safely with AGS patients around the world to reduce overt symptoms, improve sleep and comfort, and maintain a neurologic stability that has allowed most to achieve new developmental milestones. JAK inhibitors remain our only safe and proven therapeutic, and our physician partners have published protocols for dosing and safety monitoring.

• JAK Inhibition (with references to treatment protocol) - https://agsaa.org/jak-inhibition

• EULAR/ACR Recommendations - https://agsaa.org/clinical-care-recommendations

Additionally, we feel it’s important to make you aware of a few key points.

• AGS is a treatable disorder that should not be considered hopeless nor primarily progressive. It is a relapsing/remitting disease that can be successfully treated and managed. Many treated with JAK inhibitors achieve astonishing outcomes.

• AGS is an immune disorder, exacerbated by immune stimulation and associated with hematologic dysfunction.

• AGS is a heterogeneous disorder. For reasons unknown, AGS may present with a high degree of variability, including within the same family. Secondary genetic factors and/or environmental factors may play a large role in determining the age of onset, degree of disability, and phenotype. AGS is difficult to define and encompasses much.

• AGS is a multisystem inflammatory disorder. Many systems and organs may be affected by chronic inflammation and therefore may also be treated with JAK inhibitors. Patients should be regularly monitored with a comprehensive metabolic panel, and disturbances in many systems (e.g. renal, hepatic, gastrointestinal) should be investigated in the context of AGS as an autoinflammatory disorder.

Thank you for seeking the best care and future for your patient. Our organization works closely with leading AGS researchers and physicians and will continue to provide updated information and guidance. Help us help you rescue the potential of all patients living with AGS by staying in contact and proactively seeking consultation.

Sincerely,
Aicardi Goutieres Syndrome Advocacy Association
info@agsaa.org

With Gratitude, In Memory of Geoffrey J. McHale

An AGS family recently lost their beloved grandfather, Geoffrey McHale. Geoffrey was grandfather to Alec Jump, one of our all-star AGS kiddos. In lieu of gifts and flowers, Mr. McHale generously requested charitable donations be made to the AGSAA. We would like to thank Geoffrey McHale, his generous family, and everyone donating on Mr. McHale’s behalf. Your generosity enables our community to keep organizing and growing to meet the significant challenges we face as families living with AGS.

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Geoff grew up in Garfield Heights, OH and served as an altar boy at St. Monica’s Catholic Church. As a teen, he was thrilled to be selected as a Cleveland Indians batboy. He graduated from St. Peter Chanel High School and earned his bachelor’s degree from John Carroll University in Ohio. Geoff proudly served for 6 years in the United States Army. He was awarded the Vietnam Service Medal, and the National Defense Service Medal, and was honorably discharged from the U.S. Army Reserves as a Captain. Geoff enjoyed a successful career as a marketing and retail services executive, including over 15 years at IRI, Inc. For many years, he served as both an Indian Guide and Cub Scout Leader. Geoff was a longtime active parishioner of St. Raphael Catholic Church in Naperville. Geoff volunteered at Edward Hospital for over 10 years in patient advocacy, including support of Veterans.

Geoff and [wife] Dee loved to travel to Cabo, in addition to their annual trip to Saugatuck, MI with his family. Their favorite nights together were spent going to the theatre enjoying Broadway shows. However, his favorite activity, was spent with his children and grandchildren, watching their sports or being a part of their activities.

Geoffrey J. McHale. July 25, 1946 - July 21, 2022

Our Bittersweet Story of an Effective Treatment Just Out of Reach

There is no cure for AGS.

There is no time machine to go back and repair the havoc it causes once triggered. But, there IS a treatment option available right now that buys us valuable time by halting the aggressive inflammatory response that causes brain, nervous system, and organ damage.

The AGSAA, AGS experts, and AGS families overwhelmingly recommend the use of a class of drugs called “JAK inhibitors” to ameliorate the consequences of AGS disease activity. A global task force of specialists with the ACR, EULAR, NIH, CHOP, GLIA and more officially determined these drugs to be beneficial.

The most widely used and studied JAK inhibitor for AGS, baricitinib (brand name Olumiant, created by big pharma co Lilly ) was repurposed to treat AGS and other related conditions. This is called “off-label” use, a highly common practice in healthcare but can cause frustrating issues with insurance, pharmacies, and doctors when the U.S. Food and Drug Administration (FDA) hasn’t given their stamp of approval. AGS was put forth for this designation in February 2020, but was not approved for reasons unknown, and has been in limbo since. While we are not permitted to advocate for a specific drug directly with the FDA, we are working on other ways to get Aicardi-Goutieres Syndrome on their radar so they fully understand our patient experience, burden of care, and why we need equitable, timely, and affordable access to the ONLY treatment option available.

If we had Alopecia, COVID-19, or Rheumatoid Arthritis we would be able to get this prescription easily, often with Lilly subsidizing it through their Lilly Cares cost assistance program which all AGS patients are excluded from. Beyond that, AGS family access is further determined by location, competence and commitment of their prescribing doctor, insurance type, income, and other factors that should never matter when it comes to keeping your child alive and well.

Help us tell this important story to Lilly to remind them of our desire to collaborate and to the media so families get the access and support they need.

Sign our petition today and join 2,300+ supporters so far!

For media inquiries: see our Media Resources and use our contact form or email info@agsaa.org.

Eli Lilly, Advance Mission to Support Debilitating Brain Disease With Proven Medication

Eli Lilly & Co, treatment with your JAK inhibitor baricitinib has proven to be a life saving and altering treatment for children and adults living with the debilitating neuroinflammatory brain disease Aicardi-Goutieres Syndrome (AGS). For reasons unknown, our community has waited without update for you to continue advocating for approval with the FDA. In the interim, AGS families around the world have struggled with cost and access issues despite compelling testimonials, published evidence of safety and efficacy, and the support and advocacy of the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR).

Advance your mission.

Engage in dialogue and partner with the community and patient advocacy group, the AGSAA.

Provide cost assistance to AGS families.

Advocate for approval with the FDA.

Read more at agsaa.org/jak-inhibition.

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AGS Families and Supporters, join us and advocate for better access to baricitinib. Share your testimonials and sign our petition. Be heard!

Patient Registry Participant Breakdown, August 2022

We’ve seen some steady growth in registry enrollment since May, with new participants joining from all around the world. We now have an IRB approved protocol and study with the flexibility to explore topics that have been validated as important and meaningful to AGS families. As such, we’ll be reporting our numbers a bit differently, indicating the number of participants within our Luna community and the number of participants that have consented to our registry study/protocol. In the future we may introduce very narrowly scoped and specific studies for collaborating with scientists, and everyone within the community will be given the choice of whether to join irrespective of their participation in our registry study.

If you find it confusing… so do we! We at the AGSAA continue to learn and practice administration of surveys and analysis. We’re learning from others as we go and planning some interesting ways to engage our community. Stay tuned for more community led exploration and opportunities for families to own questions and answers.

Introducing AGSAA Grant Awardee, Dr. Barney Viengkhou

Dr. Barney Viengkhou is a postdoctoral fellow and PhD graduate whose research involves studying the cellular mechanisms involved in interferon-alpha mediated brain diseases. During his PhD, he has identified that endothelial cells are driving pathophysiology in mice with chronic overproduction of interferon-alpha in the brain, which forms the basis of his application.

Dr. Barney Viengkhou discusses his work with AGS.

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Are the changes to brain vasculature in Aicardi-Goutières syndrome mirrored in mice with chronic interferon-alpha production in the brain?

PI: Barney Viengkhou

ABSTRACT/SUMMARY OF PROJECT

The genetic basis of Aicardi-Goutières syndrome (AGS) involves several genes. Although several animal models replicate these genetic changes, they all have largely failed to mirror the symptomology and neuropathology observed in patients. Despite the number of genes associated with AGS, a common feature in patients is the presence of chronically elevated interferon- in the brain. Importantly, transgenic mice that chronically overproduce interferon- in the brain mirror the disease and brain pathology observed in patients with AGS. We previously identified that the brain vasculature is primarily mediating the pathology in the transgenic mice. This project will translate the mouse findings to the human disease by characterizing and investigating the morphological and molecular changes in the brain vasculature. Currently, there is no cure for AGS and treatments largely manage symptoms. Hence, demonstrating that the blood vessels of the brain are similarly affected in mice and humans is critical for understanding the cellular mechanisms of disease but also enables these mice to be utilized to develop and test new treatment strategies for AGS.

Driving Newborn Screening To The Next Stage

The AGSAA is launching a drive to collect leftover Newborn Screening (NBS) cards to advance an AGS newborn screening test! When infants are born, doctors collect and dry a few drops of blood on a paper card, to be screened for treatable disorders. It takes years for a disorder’s test to make it to primetime, as it goes through extensive lab development and validation, a pilot program, and extensive review before inclusion in official recommendations. The AGSAA along with our partners at CHOP aim to collect enough samples by the end of the year to validate a test in development. Help us collect 50 new cards by year’s end!

Here’s how you can help:

• If you’re in the USA, lookup your state’s NBS card retention policy at Baby's First Test to see if your child’s NBS card is available in storage.

• Contact the AGSAA at info@agsaa.org whether your child’s NBS card is still available or you’re unsure. Include your child’s name, date of birth, and birthplace; and our team do all the work and prepare the forms for you.

• Lastly, sign the forms and consent to CHOP collecting the card!

A Helping Hand When You Need it Most

The AGSAA has prioritized direct and meaningful support to families affected by AIcardi Goutieres Syndrome. We’d like to remind our families of a program we began at the end of 2021 to give you a lift during difficult times. Many of us understand the challenges associated with a break in routine, how a an unexpected illness or hospitalization takes a toll that extends beyond the initial event. Simply put, we’re stretched thin and could use a helping hand when these circumstances arise. The AGSAA wants to be there for you. Using funds raised by our community of allies, we’ll send you a gift card for a meal delivery service.

To date, we’ve delivered meal cards at a total of $1,300 USD. But we have more cards to send! You can help support us, this program, and your AGS friends by letting us know at support@agsaa.org when you see a family experiencing any kind of hardship.

AGS Patient Registry Virtual Walkthrough, Enrolling and Participating

Join the AGSAA’s Research Director Patrick Winters for a hands-on virtual walkthrough of the AGS Patient Registry.

We'll be holding 3 online meetings to accommodate different time zones around the globe on Saturday, August 6th. Patrick will host to help you enroll and participate in the registry or to answer questions like "why is this important?" and "how do you protect my privacy?" See the available times and meeting details on our AGSAA FB events page.

In advance of the virtual event, please watch our walkthrough video. Translated subtitles provided.

Introducing AGSAA Grant Awardee, Dr. Jessica Garau

Dr. Jessica Garau is a postdoctoral researcher at IRCCS Mondino Foundation in Pavia, Italy. She has been working on Aicardi-Goutières Syndrome since 2015, first as an undergraduate and then as a PhD student. After obtaining a PhD in Biomedical Sciences in 2020, Dr Garau is now a researcher committed to genetic and molecular characterization of rare genetic neurological diseases.

Dr. Jessica Garau discussed her work with AGS.

Dr. Garau will spend the second half of 2022 exploring potential causes of the high degree of variability in AGS as awardee of our Rare Researcher ECR Grant (project title and summary provided below). Many families are aware that AGS can present with varying degrees of severity and symptoms, even between siblings that share the same AGS causing mutations. Using AGS patient samples and data already available at the Mondino Foundation, Dr. Garau will take a careful look at the genomes and gene expression profiles of AGS individuals that share identical RNASEH2B mutations in an effort to pinpoint additional genes or variations that contribute to the development of mild vs severe outcomes. Regardless of her findings, this important work will provide insights into the factors that give rise to AGS and help guide our efforts to anticipate needs and identify targets for new therapies. The AGSAA will hold an event towards the end of 2022, inviting Dr. Garau and our community to discuss her project and work. We wish her good luck and good science!

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Transcriptome and Exome analysis of RNASEH2B patients with heterogeneous phenotypes

PI Name: Dr. Jessica Garau, PhD

Abstract/Summary of Project

Aicardi-Goutières syndrome (AGS) is a rare early-onset genetic neuroinflammatory disorder following recessive or dominant inheritance. AGS patients exhibit symptoms including acquired or congenital microcephaly, cerebral calcification, white matter abnormalities, and cerebral atrophy from birth or develop them within their first year of life. To date, mutations in nine genes have been discovered as pathogenic, all of which encode for proteins involved in nucleic acid-sensing and/or metabolism. AGS- associated mutations in these genes result in an accumulation of endogenous DNA, RNA:DNA hybrids, and/or double-stranded RNA (dsRNA) that are recognized as “foreign” and trigger type I interferon- mediated immune responses, analogous to anti-viral responses and led to classification as “primary type I interferonopathies”. Though defined by identical disease-causing mutations, clinical presentations of AGS patients can vary significantly, even within families. Thus, additional modifying molecular pathomechanisms are likely, including the coexistence of additional genomic variants or altered expression of coding and non-coding RNAs. However, scientific evidence for these hypotheses is currently lacking. In the study proposed, we aim to define molecular modifiers of disease in AGS patients with the p.A177T mutation in RNASEH2B, the most common variant seen in our group, but with different phenotypes (mild and severe). Molecular targets include: 1) Analysis of coding and non-coding RNAs by RNA-Seq or RT-qPCR 2) Analysis of patients’ exomes to identify possible digenic variants

AGS Patient Registry Introduction and Perspective

An introduction to the AGS patient Registry (https://agsaa.org/ags-patient-registry) by the AGSAA's Research Director, Patrick Winters.

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Transcription:

Hi, everyone. I wanted to introduce myself and take a moment to give you some perspective on the AGS patient registry managed by the Aicardi Goutieres Syndrome Advocacy Association (the AGSAA). My name is Patrick, and I've taken on the responsibility of research director at the AGSAA. I'm a father of three children, the youngest of which has been impacted significantly by AGS. From the very beginning of this journey, I've dedicated myself to understanding this disease and working towards solutions to improve my daughter's care. I've recently taken the lead in communications and collaborations with scientists and clinicians working on AGS. And, one of the most important and compelling things we can offer potential collaborators is coordinated access to patients, data, samples, et cetera. This registry represents and reflects our rare disease community's level of organization. A scientist looking to research a disorder or a drug company evaluating the cost of pursuing treatments for a disease will consider this in their decisions. Over the next year I've volunteered to serve as co-chair for the Global Leukodystrophy Initiative's Coalition of Patient Advocacy Groups. In my involvement with GLIA, the National Institute of Health in the U.S. , and the Rare Disease Clinical Research Network, I'll be working to help other rare disease groups prepare themselves for clinical trials by establishing registries, just like ours.

The establishment of a patient registry is the number one recommendation made by these institutions. It's the most important thing advocacy groups can do to prepare for the development of future clinical trials. Since we launched the registry, we've tried to focus surveys on data and topics that would allow us to provide useful information to families quickly and directly. By doing so, we've hoped to build a group of engaged and active participants, a necessary precursor to attracting scientists for more in depth research.

Still, I believe there's compelling work and novel insights that we can publish directly. For example, our triggers and flare survey, which is open now, will allow us to publish a full and detailed characterization of AGS disease flares. And, this is something that isn't currently written about nor well understood by families or their doctors. I'd also like to comment on data and access and visibility. None of us. And I mean it, none of us have the ability to view your name, email address, or any other personally identifiable information. Luna, the software service we use, ensures that our registry remains anonymous to us and to every collaborator that we may invite to analyze the data. All of this puts our registry above board, making it compelling to a researcher that would be able to include registry information directly in their publications.

Our registry is official in that sense, it's considered reliable; and with it we're going to advance understanding and care for AGS. So we invite all families around the world to participate. Although we acknowledge that there will be some friction and shortcomings at times, we are still dedicated to making this an inclusive and comprehensive tool for our community.

I encourage and implore you to participate.

Documenting and Characterizing AGS Triggers and their Consequences

After a bit of a delay to provide translations in multiple languages, we’re finally launching a patient registry survey to systematically document the AGS community’s experiences with what we refer to as “triggers” and “flares”. AGS is often described in outdated literature as involving a single but severe neurological regression. However, the patient community knows well that many with AGS suffer recurring periods of heightened disease activity. Unsurprisingly, these periods (or “flares”) appear to be the result of immune stimulating factors (or “triggers”); but the characteristics and severity of these flares and triggers have been mostly passed around as community anecdotes. By systematically collecting this information through our registry, we will achieve two primary goals:

• Characterize disease related stimulus and risk factors for AGS families.

• Identify distinct phenotypes, perhaps related to genotype, AGS Scale score, or frequency + severity of relapse.

With this new survey and previously collected data, we hope to begin to answer everyone’s first question, “what will happen to my child?” While this will be our longest survey to date, we hope that you’ll see the benefit that all of this information will provide to you and others.

Modeling Areas of Concern for AGS Families, Stage 2

We’ve completed the first stage of the Community Driven Innovation (CDI) process with Luna. The AGSAA has a list of topics ranked in order of importance to AGS individuals and their families that will help guide our future surveys and investigations. Additionally, our IRB and study protocol allows us to move forward with surveys on these topics without the red tape of protocol amendments (our AGS Retrospective Triggers and Flares survey is our first example). Now that we’ve reached statistical significance with our responses to this initial ranking, we’re moving on to stage 2, an effort to build a mental model of these concerns. We’re asking AGS individuals and families to organize the list of topics into groups in whichever way makes sense to them. With this type of activity, we’ll not only have an understanding of what topics relate to each other; but we hope to identify distinct ways that families think of AGS. With a disease as heterogeneous as AGS and with adults and children living with varying medical concerns and degrees of disability, we expect to see multiple, distinct models emerge from the results. While we might intuitively expect this and assume the differences to be related to disease severity, we really have no idea! By completing this latest survey activity, we’ll not only know what topics are important overall, but we’ll know who they are important to (by age, genotype, etc.).

Please note that this survey will be conducted in optimalworkshop.com (outside of our patient registry at lunadna.com). The responses are being collected by the AGSAA and Luna but we require additional software to complete the grouping activity that is unavailable in LunaDNA at the moment.

The list of AGS concerns/topics in ranked order of importance to patient registry participants:

• Muscle tone management

• Flare-ups (triggers, mitigation, frequency)

• Availability of Treatments

• Other Illness impacts (colds, UTI’s)

• Therapies (PT, speech, nutrition)

• White matter (degradation, improvements)

• Dysautonomia

• Education Support (IEP, accessibility devices)

• Interferons (levels, control)

• JAK inhibitors (Baracitinib and related)

• Mobility (issues, progression)

• Atypical presentation(s) of AGS

• Immune support

• Mutation Specific Information

• Newborn screening

• Proactive intervention vs reactive

• Assistive technology

• Brain-body connection

• Communication

• Nutrition

• Pain management

• Patterns in condition (weeks, months, years)

• Physical Developmental delays or regression

• Prognosis (months, years)

• Socialization and friends

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.