Strides in STXBP1 Research Jan/Feb

Welcome back to another year of Strides in STXBP1 Research.

So, what’s new in January and February of 2025?

Chinese scientists examined white blood cells, called neutrophils, that can predict recovery after a stroke. Neutrophils at a type of white blood cell that are densely packed with what are called ‘secretory granules’. They are important in fighting off infections as they can release substances into the environment, though a process called ‘degranulation’, and these substances can attack bacteria. Neutrophils that become overactive result in excessive degranulation, which is associated with many inflammatory disorders. Excessive degranulation of neutrophils is also associated with a poor outcome from a stroke and the scientists were interested in seeing what proteins might be associated with causing degranulation following a stroke and STXBP1 was one of three proteins they identified. Since the release of neutrophil secretory granules is similar to the release of neurotransmitters from neurons, this makes sense. They then found that the activity of the three identified proteins (including STXBP1) were themselves influenced by another protein called HDAC2, and when HDAC2 was inhibited, the levels of the three proteins were increased. This finding is very interesting because the drug phenylbutyrate, which is the active substance in Ravicti (recall the Ravicti trial for STXBP1-RD being conducted by Zach Grinspan), is also known to inhibit HDAC2.

A group of Argentinian researchers published a retrospective study of 24 children diagnosed with infantile epileptic spasms syndrome (IESS). They found that a genetic cause could identified in 12 of the children, including one child identified with a variant in STXBP1.

Squamous cell carcinoma is a type of lung cancer that has a low 5-year survival rate. A Chinese group of researchers compared cancerous lung tissues to normal tissues and found many genes that were either more or less active in cancer cells. They identified two key molecules (MAGI2-AS3 and MBNL2) that seem to play important roles in this type of lung cancer. MAG12-AS3 is a type of molecule known as a long non-coding RNA (lncRNA). These types of molecules can control the expression of various messenger RNAs (mRNAs) and thus the expression of various proteins. One mRNA and protein that MAG12-AS3 appears to control is STXBP1. While the authors of the paper did not ultimately consider STXBP1 levels as a prognostic marker for squamous cell lung cancer, high expression levels were associated with lower overall survival in their patient population.

I wanted to draw attention to one additional paper that was published. A group from Antwerp University in Belgium published their research characterizing the gait of individuals with Dravet Syndrome (DS), Helsmoortel-Van Der Aa Syndrome (HVDAS), or Tuberous Sclerosis Complex (TSC); three genetic conditions with similar symptoms to STXBP1-RD. Gait refers to the manner of walking, or how a person moves their legs and body during locomotion. The team identified differences in gait between neurotypical controls and the genetic disorders as well as differences between the genetic disorders themselves. One of the authors of the paper is supported by a grant from the Million Dollar Bike Ride (MDBR) and our Foundation and similar gait studies are currently being performed in kids with STXBP1-RD.