Scales. Decades of cerebral palsy research suddenly become meaningful for STXBP1 and SYNGAP1. The CP field has built a mature framework of classification systems such as the Gross Motor Function Classification System (GMFCS), along with related tools for manual ability and communication. These systems were not developed for synaptic disorders, which were largely unknown when these scales were first conceptualized. However, as we move toward trial readiness, they offer exactly what we need: structured ways to describe function. The question is whether they translate and can be used. Here is what we found.
Tag Archives: STXBP1
UNC13A and the gate of synaptic release
Fusion. If you have ever tried to merge soap bubbles, you know the paradox. Soap bubbles look soft and fragile, but the moment you bring them close, they push each other away. Membranes behave similarly. A synaptic vesicle and the presynaptic membrane do not naturally want to merge. They repel each other. Therefore, synaptic vesicle release requires a mechanism that overcomes this resistance, holds two membranes in close contact, and then triggers fusion on demand within milliseconds. In a recent paper, that mechanism is brought into focus through UNC13A, a gene encoding one of the central priming factors that makes synaptic fusion possible. Here is what the study shows.
Signals in the noise – qEEG patterns in genetic epilepsies
qEEG. The electroencephalogram is one of the oldest tools in neurology. We use it every day to diagnose and monitor brain function, yet, even in the era of genomic medicine, most of our EEG interpretation still relies on visual inspection, a human reading of squiggled traces. In a recent publication in Neurology, we asked whether the information embedded in these signals could be measured more objectively in children with STXBP1, SCN1A, and SYNGAP1-related disorders. Here is the story on how we identified hidden signals in the EEG tracings of individuals with genetic epilepsies.
The rare disease with fastest growing knowledge – the 2025 STXBP1 Summit+
Westminster. The Westin in Westminster, Colorado has an inbuilt alarm clock. As the hotel is a relatively isolated tall building, you get the most intense sunrise over the big Colorado sky that gently wakes you up as it intensifies – a consolation prize if your hotel room doesn’t have the majestic mountain view, as was my case this year. The Westin the venue for this year’s STXBP1 Summit+ Family Meeting. Here are three takeaways from the summit, from my perspective as a clinician researcher.
The 70-mile synapse – riding for Lulu’s Crew
MDBR 2025. Imagine a sugar cube-sized piece of our brain. Within this small segment of neuronal tissue, the total length of nerve fibers amounts to approximately 70 miles. This is exactly the distance I rode for the 2025 Million Dollar Bike Ride last Saturday as a member of Lulu’s Crew. Here is my blog post on a different kind of fundraising for rare disease research, the type of advocacy that has raised more than a million dollars for STXBP1 in the last seven years while making your legs feel like Jello.
STXBP1 and SYNGAP1 Natural History – Reflections after Day 1 of ENDD Clinic
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 – here is what you need to know in 2023
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.
The future of biomarker development in rare disease
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.
Artificial intelligence in epilepsy – the rare disease perspective
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.
The pebbles of Demosthenes – stuttering genetics in 2023
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