The surprising discovery earlier this year that it was possible, in a lab dish, to shut down the extra copy of a chromosome that causes Down syndrome ignited hopes that the technique could one day be developed into a therapy. The scientist who led the work, Jeanne Lawrence of the University of Massachusetts Medical School, cautioned that such a prospect was exciting, but that many years of work would be needed before the method could even be tested in people.
Lawrence sat down with a small group of reporters at the American Society of Human Genetics meeting taking place in Boston on Tuesday afternoon to give a hint of how her research is progressing. In the near term, Lawrence hopes her work will provide a powerful new approach to tease out the biology of Down syndrome, yielding new insight about what exactly goes wrong within cells. Those insights could lead to the development of drugs, and her technology could provide a sample of cells on which to test and screen new therapies.
Lawrence said that her new data are preliminary, but that an intriguing finding had emerged. Lawrence silenced the extra copy of the chromosome in stem cells made from people with Down syndrome and compared them with cells with the normal two copies of the chromosome. Looking side by side allows her to see what the differences are in gene activity between the two types of cells. To her surprise, the biggest magnitude changes are not in the activity of genes found on the extra chromosome; the most-affected genes are scattered on other chromosomes, suggesting that the condition may stem from the way that the extra chromosome regulates gene activity on other, normal chromosomes.
“We’re hopeful this is a way to narrow in on what are the genes that are the most perturbed,” Lawrence said. “You could do it in various cell types and ask what is going wrong in heart muscle that might contribute to general heart defects, or what’s going wrong when you differentiate neurons.”
Lawrence is also testing whether her technique works in living animals—and if it does, to see what effects it has on their behavior and development. She is trying to silence the extra chromosome in the cells of two types of mice that have been engineered to suffer from a version of Down syndrome.
She said that her laboratory has been a little overwhelmed with requests to share her cell lines—something that she would very much like to do but that is taxing her resources. UMass Medical School did have a stem cell bank, funded through the state's biotech bill, but it shut down last year, to the disappointment of stem cell scientists. Lawrence hopes that perhaps it will be possible to reignite the stem cell bank, with a more specific focus on disease-specific cell lines.
She also spoke a little about the far-off possibility of developing a chromosome-silencing therapy. If the technique is developed to the point where human tests could be considered, she said the most likely candidates for testing would likely be other chromosomal disorders that are far more severe than Down syndrome—trisomy 13 and 18.