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 AGS is often described in outdated literature as involving a single but severe neurological regression.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