Strides in STXBP1 Research
What’s new in August of 2026
Italian researchers and clinicians examined brain MRI scans from 24 children with STXBP1-RD and compared the scans to scan taken of 48 typically developing children in order to understand how this disorder may affect brain structure. Compared with typically developing children, those with STXBP1-RD showed thickening in some regions of the cortex, which is the outer layer of the brain, or the area that contains primarily neurons. They also found somewhat smaller surface area in the front and rear of the brain and reduced volume of the ‘white matter’, which contains the connections between different regions of the brain. These changes suggest that there may be disrupted brain growth and connectivity in STXers, though the differences observed were generally subtle. Some STXBP1-RD children also had subtle signs of focal cortical dysplasia, a developmental abnormality confirmed by surgery in two cases. The researchers found that more severe intellectual disability was linked to larger ventricles (the fluid-filled spaces in the brain) and greater white-matter loss. Overall, the findings show that STXBP1-RD is associated with widespread subtle, but measurable, differences in brain development that may help explain the condition’s cognitive and neurological challenges.
Researchers from China examined eight different STXBP1 genetic variants to understand why some people develop very severe epilepsies while others have much milder forms. Most of the identified variants caused early-onset, hard-to-treat epilepsy with significant developmental challenges, and these severe variants tended to strongly disrupt the structure or stability of the STXBP1 protein, leading to much lower levels of the protein in lab tests (haploinsufficiency). Two variants, however, were found in families with milder epilepsy and normal development, and these caused only small changes to the protein’s structure and did not significantly reduce protein levels. Overall, the study shows that the degree of protein disruption closely matches how severe a person’s symptoms are.
STXBP1, also known as Munc18-1, is necessary for the release of neurotransmitters from neurons; however, it also is involved in the release of insulin from pancreas cells as is a similar protein, Munc18-2. Swedish researchers looked at how these two proteins, Munc18-1 and Munc18-2, help insulin-producing cells release insulin. Like in neurons, these proteins work with another protein, syntaxin, to first “dock” insulin granules at the cell membrane and then “prime” them so they can fuse and release insulin when the cell is signaled to do so. By deleting one or both Munc18 proteins in insulin-secreting cells, the researchers found that losing Munc18-1 almost completely blocked insulin release, while losing both proteins also made granules less stably “docked” to the membrane. Adding back either protein restored function, though Munc18-1 was better at supporting the priming step. Microscopic imaging of the insulin releasing cells showed that both Munc18 proteins can be seen together with syntaxin at the release site, but Munc18-1 binds more strongly, helping organize the machinery needed for insulin secretion. Overall, the work shows that the two Munc18 proteins have overlapping but distinct roles, with Munc18-1 being especially important for preparing granules to release insulin.
Previous studies have shown that a reduction in STXBP1 gene expression is associated with a poor prognosis in patients with triple negative breast cancer (TNBC), but no one knows exactly why. Researchers from China increased STXBP1 protein levels in breast cancer cells and found that the cells grew more slowly and showed more signs of programmed cell death. By analyzing gene activity, they found that STXBP1 changes how many genes are switched on or off and including key DNA-repair genes. Radiation therapy is a key treatment for TNBC, and these DNA-repair genes can be used by cancer cells to repair radiation-induced DNA damage. STXBP1 appears to disrupt DNA-repair genes in breast cancer cells, thus making them more sensitive to radiation.
A review article from the University of Arkansas focused on early infantile developmental and epileptic encephalopathy (EIDEE), one of the most severe forms of epilepsy beginning in the first three months of life. Babies with EIDEE have frequent hard-to-treat seizures, major developmental challenges, and a very abnormal EEG pattern called burst-suppression. The article reviews the importance of diagnosing the underlying cause of EIDEE and provides a useful ‘algorithm’ that doctors can use to do so. The condition can be caused by many underlying problems—genetic changes (especially in genes like STXBP1, KCNQ2, SCN2A), metabolic disorders that respond to vitamins, or structural brain differences. Diagnosis relies on EEG, brain imaging, metabolic testing, and early genetic sequencing, which now identifies a cause in most cases. Proper diagnosis can lead to specific treatments including antiseizure medications, vitamin therapies for specific metabolic causes, ketogenic diet, and sometimes epilepsy surgery when a structural problem is present. Overall, outcomes depend heavily on the underlying cause, with vitamin-responsive forms having the best prognosis and most other forms leading to persistent seizures and significant developmental disability. A separate review article from Italy also looked at neonatal encephalopathy (EIDEE is a specific type of neonatal encephalopathy) and how important genomic testing is in distinguishing it from a different disorder called hypoxic-ischemic encephalopathy (HIE), which is a brain injury caused by reduced or stopped oxygen and blood flow to the brain in newborns.
