Strides in STXBP1 Research: April/May
An interesting paper on the ethics of disease-modifying therapies was published by a team from the Netherlands. The article explores why some parents of children with rare genetic neurodevelopmental disorders—such as STXBP1 and Kleefstra syndrome—feel torn about emerging disease-modifying and disease-altering treatments that aim to change how their child develops. While most parents hope these therapies could help their child gain skills, independence, or comfort, some worry that treatment might also change “who their child is.” Through interviews, the authors identify four types of concerns: whether treatment will help a child grow into their best self, whether it might instead make the child feel unlike themselves, whether changes could disrupt the family’s established ways of relating to the child, and whether pursuing treatment reinforces harmful societal messages that children with disabilities need to be “fixed.” The paper argues that these identity related worries are real, nuanced, and important for clinicians and researchers to discuss openly with families as new therapies and clinical trials emerge.
A group of physicians from Singapore published a small case series report describing four children with STXBP1-RD; two of the children carried newly identified STXBP1 variants. Their symptoms ranged from mild delays with well controlled seizures to very severe disability with daily seizures and painful muscle tightening. One child with the most severe symptoms and refractory seizures showed a remarkable response to cannabidiol (CBD); her seizures stopped, and her dystonia improved significantly without side effects. The authors highlight the variability of symptoms among people with STXBP1-RD and suggest that CBD may be a promising treatment option for those with hard to control seizures and movement disorders.
Ulcerative colitis (UC) is a long‑term inflammatory disease of the colon. A group of Chinese researchers studied how disruptions in the body’s internal clock, our circadian rhythm, may play a role in how UC develops and worsens. By analyzing large datasets of colon tissue and single cells from people with UC, the researchers found hundreds of genes linked to circadian rhythm problems that were also tied to inflammation, immune cell changes, and tissue damage. They identified 12 key genes, including STXBP1, that strongly predicted UC and were active in cell types involved in inflammation. The researchers hypothesized that disturbances in the circadian rhythm resulted in an increase in inflammation of the colon and that STXBP1 plays a role in this. To test their hypothesis, they induced UC in mice and demonstrated the mice had a significant increase in STXBP1 RNA in their colon tissue.
Endometriosis (EM) is another chronic inflammatory disease where tissue similar to the lining of the uterus grows outside the uterus. It afflicts millions of women yet despite its prevalence it can be had to diagnose due to the lack of specific symptoms and available biomarkers. Researchers from China used large genetic and protein datasets coupled to lifestyle and health information from thousands of people to try to identify potential blood biomarkers of EM risk. They identified five proteins, including STXBP1, whose levels appear to influence a person’s risk of developing EM. They found that lower levels of blood plasma STXBP1 is associated with EM and postulated that a dysregulation of STXBP1 may underlie the chronic pain and/or neuroinflammation observed in EM.
