The Global Down Syndrome Foundation has funded a landmark study led by scientist Dr. Joaquín Espinosa, Associate Director for Science at the Linda Crnic Institute for Down Syndrome. The results of the study were published online by eLife, an open-access life sciences and biomedical research journal targeted at the very high end and run by scientists including Nobel Laureate and Editor-in-Chief, Randy Schekman. The journal was established by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.
Dr. Espinosa's paper in eLife, "Trisomy 21 Consistently Activates the Interferon Response," shows the unequivocal impact of trisomy 21 (the triplication of chromosome 21 that causes Down syndrome) on interferon (IFN) signaling. Specifically, cells with trisomy 21 produce high levels of interferon-stimulated genes and lower levels of genes required for protein synthesis.
Interferons are molecules produced by cells in response to viral or bacterial infection, and which act on neighboring cells to prevent the spread of the infection, shut down protein synthesis, and activate the immune system. The paper posits that if interferons are constantly activated, then the body is constantly fighting a viral infection even when such infection does not exist; this would likely cause many damaging side-effects.
Down syndrome is caused by having three copies of chromosome 21 instead of two, and since four of the six interferon receptors -- the proteins that sense the presence of interferons -- are encoded on chromosome 21, cells with trisomy 21 react more strongly to small amounts of interferons in their microenvironment.
Dr. Joaquín Espinosa is enthusiastic about the results of his study, "The constant activation of the Interferon response could explain many aspects of Down syndrome, such as cognitive deficit, stunted growth, increased prevalence of autoimmune disorders, high risk of Alzheimer's disease, and protection against solid tumors."
Dr. Kelly Sullivan, lead author of the paper, has already embarked on follow up studies. "The next steps are to fully define the role of the interferon response in the development of Down syndrome using mouse models. The great news is that FDA-approved drugs that block the interferon pathway already exist. Much clinical research will be needed to determine whether those drugs are safe over a long period and have therapeutic benefits for people with Down syndrome," said Sullivan.
"In principle, the findings are tremendously exciting and present a novel view of some of the characteristic features associated with trisomy 21," said Christopher Glass, MD, PhD, University of San Diego California School of Medicine, an eLife editor who reviewed Dr. Espinosa's research.
Other scientists on the eLife review board were also impressed with the results of Dr. Espinosa's research publicly stating: "These findings have important implications for understanding the basic nature of, and individual variation in, the diverse phenotypes of people with Down syndrome," and "This is clearly an interesting and significant study that provides important new insights into the differences in gene expression in trisomy 21 cells."
Dr. Espinosa's research started with a Crnic Grand Challenge Grant organized by the Executive Director of the Crnic Institute, Dr. Tom Blumenthal. "One cannot overemphasize the importance of the funding from the Global Down Syndrome Foundation and the research being conducted at the Crnic Institute for Down Syndrome," said Dr. Tom Blumenthal, Executive Director at the Crnic Institute. "Having attracted 30 labs and over 100 scientists, including Dr. Espinosa, we have created an incubator for accelerated research that is already pointing to discoveries that have the potential to enhance the quality of life for people with Down syndrome and millions of typical people as well."
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