NEW: UMass Scientists Have Breakthrough on Down Syndrome Research
Thursday, July 18, 2013
Scientists at UMass Medical School are the first to establish that a naturally occurring X chromosome “off switch” can be rerouted to neutralize the extra chromosome responsible for trisomy 21, also known as Down syndrome, a genetic disorder characterized by cognitive impairment.
The discovery provides the first evidence that the underlying genetic defect responsible for Down syndrome can be suppressed in cells in culture (in vitro). This paves the way for researchers to study the cell pathologies and identify genome-wide pathways implicated in the disorder, a goal that has so far proven elusive. Doing so will improve scientists’ understanding of the basic biology underlying Down syndrome and may one day help establish potential therapeutic targets for future therapies. Details of the study by Jiang et al. were published online in Nature.
“The last decade has seen great advances in efforts to correct single-gene disorders, beginning with cells in vitro and in several cases advancing to in vivo and clinical trials,” said lead author Jeanne B. Lawrence, PhD, professor of cell & developmental biology. “By contrast, genetic correction of hundreds of genes across an entire extra chromosome has remained outside the realm of possibility. Our hope is that for individuals living with Down syndrome, this proof-of-principal opens up multiple exciting new avenues for studying the disorder now, and brings into the realm of consideration research on the concept of ‘ ‘chromosome therapy’ in the future.”
Jun Jiang, PhD, instructor of cell and developmental biology at UMMS, came to work with Dr. Lawrence in 2009 and began a research project to insert the XIST gene into one chromosome 21 – supported by NIH funding for high-risk, high-impact work.
This finding opens multiple new avenues for translational scientists to study Down syndrome in ways not previously possible. Determining the underlying cell pathologies and gene pathways responsible for the syndrome has previously proven difficult, because of the complexity of the disorder and the normal genetic and epigenetic variation between people and cells.
“This highlights the potential of this new experimental model to study a host of different questions in different human cell-types, and in Down syndrome mouse models,” said Lawrence.
“We now have a powerful tool for identifying and studying the cellular pathologies and pathways impacted directly due to over-expression of chromosome 21.”
“Dr. Lawrence has harnessed the power of a natural process to target abnormal gene expression in cells that have an aberrant number of chromosomes,” said Anthony Carter, PhD, of the National Institutes of Health’s National Institute of General Medical Sciences, which partly supported the study. “Her work provides a new tool that could yield novel insights into how genes are silenced on a chromosomal scale, and into the pathological processes associated with chromosome disorders such as Down syndrome.”
New discoveries made using this approach could one day identify new therapeutics for chromosome disorders like Down syndrome.
“In the short term the correction of Down syndrome cells in culture accelerates the study of cell pathology and translational research into therapeutics, but also for the longer-term, potential development of ‘chromosome therapies,’ which utilize epigenetic strategies to regulate chromosomes, is now at least conceivable. Since therapeutic strategies for common chromosomal abnormalities like Down syndrome have received too little attention for too long, for the sake of millions of patients and their families across the U.S. and the world, we ought to try,” said Lawrence.
Lawrence and colleagues will now use this technology to test whether chromosome therapy can correct the pathologies seen in mouse models of Down syndrome.
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