February 24th is international SCN2A awareness day! This week we recognize the individuals and families affected by SCN2A and share some insights into new science coming out of our lab.

Two different presentations of SCN2A: In the past few years, we have learned more about different possible presentations (which scientists often call "phenotypes") of SCN2A.

The COVID-19 pandemic created in obstacle in seeing more participants for our BioGENE study, but we are excited to debut some preliminary results related to our resting state biomarker. We submitted an abstract to the International Society for Autism Research (INSAR) looking at underlying brain responses from resting state EEG. Here, we were looking to see if there are differences across spectral frequencies that reflect varying brain states -- with a special focus of looking more at the differences between loss-of-function (LOF) and gain-of-function (GOF) mutations.

How do we know if a variant is LOF/GOF?: To know for certain whether a person's genetic mutation is LOF/GOF, it is important to identify each variant's function using molecular neuroscience and cellular electrophysiology to test what happens in a neuron. We use scalp electrophysiology , which measures ALL the neurons instead of one at a time. Although many variants have been tested and are known to be LOF/GOF,  we do not know the status for ALL of our participants. Instead, we work from the assumption that participants with a presentation of infantile epileptic encephalopathy (+IEE or "with IEE") or other disruptive seizures during early development (<12 months of age) may have a GOF mutation. And those that do NOT have IEE (-IEE) may have a LOF mutation. 

Study design: Our participants watched screensaver-like videos while we recorded electrical signals using electroencephalography (EEG) using a wet net with over 120 recording locations. We take the raw signal and extract out information related to overall/broad brain states -- delta (deep sleep, slow rhythms), theta (daydreaming,  moderate rhythms), alpha (reflection after a task, fast rhythms), and beta (engagement, fastest rhythms). 

Study results: We found that:

• Unique pattern for SCN2A group related to slower rhythms (delta and theta)
  • -IEE SCN2A participants (likely LOF) had the most delta and theta rhythms 
  • +IEE SCN2A participants (likely GOF) had greater delta and theta relative to autism and neurotypical control groups
• Alpha rhythms were greater for +IEE SCN2A participants
• Beta rhythms were different for SCN2A groups
  • -IEE SCN2A participants (likely LOF) had more beta than an autism group with average IQ
  • +IEE SCN2A participants (likely GOF) had more beta than autism and neurotypical groups

What does this mean?: Some of these findings relate to other work characterizing brain states in adults with a more broad or "generalized" epilepsy (for instance, see this study from 2000). It is encouraging that the SCN2A participants have distinct profiles relative to our control groups. To feel more confident in our findings, we will continue to add additional participants to our study. 

Next steps:

1. We are hoping to add a few more families to the study, as soon as our university resumes permission for off-campus research. Be on the look out for more details as Dr. Hudac plans a COVID-safe, 1-woman research road trip in Summer and Fall of this year! 
2. We want to keep working to think through how SCN2A biomarkers may help separate between the two different presentations. We are working to learn more about resting state in the context of other populations with epilepsy.
3. This summer, graduate student Nicole Friedman, will be completing our analyses and preparing these data for publication. We will update as these results are finalized!  

We are getting ready to relaunch our research after stopping human subject work due to COVID-19 precautions. Here is what we are working on:

1. Step 1: Safety plan.  We made a comprehensive safety plan describing our strategies to reduce COVID-19 risks. You can find information regarding our safety plan on the COVID-19 page.
2. Step 2: University approval. We have submitted this plan to the University of Alabama for approval. We are not 100% certain about how long this will take, but our colleagues are working very hard to help us in this process.
3. Step 3: Schedule visits when safe. We will work with families to determine an optimal research visit plan. We will follow state and local guidance about out-of-state travelers and will carefully monitor COVID-19 numbers. It's ok if we have to reschedule last minute due to increasing concerns -- we'll be very flexible! 

If you are (still) interested in participating in the BioGENE study, we would appreciate if you would fill out this survey so that we can learn about your own personal concerns and begin to think through logistics. 
BioGENE_Study_COVID

Can't wait to see everyone! We are thinking about you and hope you are doing well
-Dr. Hudac & the B-RAD Lab

In early August 2019, Dr. Hudac presented at the 3rd Annual SCN2A Family and Professional Conference in Seattle, WA.  Watch her talk on "Human Brain Markers in SCN2A" below and check out more of the talks on the FamiliesSCN2A Website.