A big step forward. Disease natural history and clinical trial readiness are constantly discussed topics in the rare genetic epilepsy space. Additionally, these concepts have driven our work in the Helbig lab since the very beginning. So why then did last week’s launch of our group’s first prospective natural history study of STXBP1 and SYNGAP1 feel like such a monumental step forward? Last week, we evaluated our first participants in the prospective natural history study that is part of the newly established Center for Epilepsy and Neurodevelopmental Disorders (ENDD), and here are some reflections from our team.
STXBP1. Today is the first day of the 1st European STXBP1 Summit and Research Roundtable, held from May 16-18th in Milan, Italy. This meeting is bringing together voices from academia, industry, organizations, and family foundations to discuss the current state of research – spanning from preclinical efforts investigating mechanisms of disease to moving towards the clinic and the future therapeutic landscape. In 2023, it feels like an understatement to say that STXBP1 is on the map. In spirit of the ongoing momentum in the field, we wanted to refresh the gene page and outline three emerging frameworks to think about STXBP1.
CNS Biomarkers. In the last two days, our team attended the Workshop for Multimodal Biomarkers in CNS Disorders held at the National Academies of Sciences, Engineering, and Medicine in Washington, DC. This conference provided a needed review of the current state of multimodal biomarker discovery and development. While most of the speakers focused on more common CNS disorders such as Alzheimer’s disease and neuropsychiatric disorders, there stands to be important lessons that can be translated into the rare disease field. Here is what we learned about the clinical utility of biomarkers and their potential as we move towards precision medicine in rare disease.
Breckenridge. This week, our team attended the first conference for Artificial Intelligence in Epilepsy in Breckenridge, Colorado. I was honored to be one of the two speakers representing the epilepsy genetics field, trying to build the bridge between the impressive amount of research in machine learning and EEG analysis with our current progress and research efforts in the genetic epilepsies. In this blog post, I would like to summarize some of my impressions from this meeting and discuss two aspects where rare disease research and machine learning already intersect, namely seizure forecasting and virtual clinical trials.
Zebra finches. Exactly one year ago, I wrote my last blog post on the genetics of stuttering and thought that it would be time for an update. Here, I would like to explore why stuttering is a truly neglected neurogenetic disorder and why we have made so little progress. In addition, I would like to give a brief update on where we are right now, looking at stuttering from the perspective of the wider pediatric neurogenetics field. In addition, we will unleash the power of EMR genomics to query the medical records of more than 52,000 individuals to find associated genes, and we will discuss a monogenic cause of familial childhood-onset fluency disorders that we did not expect to find. Here is a summary of the last 12 months in stuttering genetics. Continue reading
Music City. This year’s Annual Meeting of the American Epilepsy Society (AES) took place in Nashville, Tennessee. With a pre-meeting in Memphis and the annual Clinical Skills Workshop as the final event of the annual meeting, our team was able to spend more than a week in the Volunteer State. Yes, there is more than enough music in Nashville and it is virtually impossible to step into a pub, restaurant, or Honky Tonk without live music. Now that my ears have recovered, here is a summary of epilepsy genetics at AES 2022. Continue reading
Understanding the EMR. Several weeks ago, I gave a presentation at the STXBP1 Summit conference, the third annual meeting since the first in 2019 – a time when I had just entered the field of neurogenetics. It has been fascinating to follow one of the neurodevelopmental genes with the “fastest growing knowledge,” with the expanded scope of clinical studies and emergence of novel avenues for targeted gene therapies on the horizon. However, one of the many projects our STXBP1 team is currently working on takes a somewhat atypical approach – we aimed to map the natural disease history of STXBP1-related disorders based entirely on reconstructed Electronic Medical Records (EMR). Here are some of the challenges we have had to confront and what we learned searching for meaning in the depth of the EMR. Continue reading
STXBP1 in Philly. From August 18-20, the STXBP1 community met in the Bellevue Hotel in Philadelphia, the first in-person summit after our initial Philadelphia meeting in 2019. Much has changed since our initial meeting – an entire scientific community has woken up to study one of the most common (and enigmatic) neurodevelopmental disorders, the STXBP1 Foundation has grown significantly in activities and scope, and there are very promising developments in the main therapeutic areas, namely drug development, antisense oligonucleotides, and gene therapy. It is not an exaggeration to say that STXBP1 is on the map in 2022 and it is one of the genes with the fastest growing knowledge. Here are my personal reflections from the 2022 STXBP1 Summit – and I want to thank our entire ENGIN team for their fantastic work during our first Synapse Clinic the day before the Summit. Continue reading
STX. We typically don’t blog about preprints, but we are making an exception this time given the upcoming STXBP1 Summit in Philadelphia on August 19-20. This is a post about one of our projects on STXBP1 that tries to understand the clinical presentation holistically, trying to find a way to capture the lived experience of families with STXBP1. In our current manuscript that will be presented at the STXBP1 Summit, we introduce our disease concept model for STXBP1. Disease concept models are formal frameworks that are increasingly required by regulatory agencies such as the FDA. Here is a brief overview what we find when we conduct formal interviews with families how a disease concept model helps us define phenotypes. Continue reading
STX. I have to admit that the main gene that our team is working on has received relatively little attention on our blog, even as several manuscripts on STXBP1 have recently been published that add to our understanding of STXBP1-related disorders. I described STXBP1 at the Simons Foundation’s INSYNC-AS meeting as one of the genes with the “fastest growing knowledge,” now following close behind recognized neurodevelopmental disorders including Rett and Angelman Syndrome. In this post, I would like to feature one of our recent publications in Neurology Genetics that assessed the developmental trajectory of 48 individuals with STXBP1-related disorders. In particular, I would like to zero in on the most important result of this study, which expands on one of the controversies in the STX field. Continue reading