Cellular response linked to Down syndrome chromosome may impair heart development in babies: Research

Scientists have observed trisomy 21, the extra copy of chromosome 21 that causes Down syndrome, a genetic condition that impairs heart formation during fetal development, a defect that causes an overactive cellular response when attacked by viruses It is made Using stem cells obtained from research participants with Down syndrome and a mouse model of the syndrome, scientists at the University of Colorado Anschutz Medical Campus in the US modeled cardiogenesis, or heart formation, in the laboratory.

The scientists demonstrated that blocking the antiviral cellular response, or interferon response, improved cardiogenesis. “We were surprised to find a strong activation of the interferon response during the differentiation of pluripotent stem cells into heart muscle cells in patients with trisomy 21,” explained Associate Professor Qunhua Song. “We now believe that the abnormally high interferon response may be associated with early cardiac development.” may be harmful to.” Medicine and lead researcher K.

Furthermore, they found, interferon hyperactivity impairs cardiogenesis by inhibiting a series of key molecular events essential for heart development, such as the Wnt signaling pathway. According to Kangwu Lee, lead author of the paper published in the journal iScience, “Too much interferon activity leads to greatly reduced Wnt signaling, which in turn impairs cardiac muscle cell function. The discovery of this cluster of events is inappropriate.” sheds light on potential strategies to improve heart formation in Down syndrome by reducing interferon signaling and/or enhancing Wnt signaling.”

Testing this therapeutic strategy in a mouse model of Down syndrome, the investigators treated pregnant female mice with JAK inhibitors, which are known to reduce the interferon response. They then monitored the effects on heart development in fetuses with the same genetic mutation as trisomy 21.

The researchers observed a significant improvement in cardiogenesis in the rats. “These are very important results, as they suggest a potential pharmacological strategy for prenatal treatment of one of the most deleterious effects of trisomy 21.

“Babies born with Down syndrome and congenital heart defects face many challenges, ranging from the need for heart surgery soon after birth to long-lasting effects on their physiology later in life Are.” However, much additional research will be needed to define this. The safety and efficacy of the use of JAK inhibitors during pregnancy, said Joaquin Espinosa, executive director of the Linda Kranick Institute for Down Syndrome at the University of Colorado and co-author of the paper.

Espinosa and his team are currently leading clinical trials studying the benefits of JAK inhibitors in older children and adults with Down syndrome. These findings, he said, expand on a growing body of evidence demonstrating the detrimental effects of interferon hyperactivity in Down syndrome, even during the earliest stages of fetal development.

The results also support the idea that many of the symptoms of Down syndrome are driven by lifelong dysregulation of the immune system, he said, and that restoring immune balance may provide therapeutic benefits.