Translating Down Syndrome find to treatment not simple

Researchers have sought to develop genetic techniques to counter common diseases since the first publication of the human genome, but very few therapies have emerged as a result. While there have been great advances in our ability to study a disease by analysing what the associated genes are doing, it is no simple matter to translate this into a working human treatment.

The team at the University of Massachusetts Medical School led by Prof Jeanne Lawrence has now done something similar in the gene-based condition Down Syndrome.

Down Syndrome is caused when a child is born with an unwanted extra copy of chromosome 21. It interferes with normal development, causing characteristic physical and cognitive changes.

Prof Lawrence and colleagues have found a way to switch off the entire superfluous copy of chromosome 21 in cell culture experiments, publishing their findings in the journal Nature. While this tells us nothing about what this might mean in a human model, being able to turn off an entire chromosome provides a highly valuable tool to researchers.

Having shown that it can be done means the technique could be reapplied in other chromosomal disorders, providing a way to model other genetic conditions. It allows the researchers a previously unprecedented view of what individual genes are doing free from the genetic “noise” associated with these studies.

They can now dig down into the basic biology taking place in Down Syndrome individuals and how this differs from those born without a third copy of chromosome 21.

It is noteworthy that the introduction of just a single gene, called Xist for X-inactivation gene, was enough to switch off the chromosome, and the hundreds of genes it contains.

Perhaps more importantly, the team found that shutting down the extra chromosome caused the remaining two copies to reverse the unusual pattern of cell growth and gene expression seen in Down Syndrome cells.

They believe that the work opens up at least the potential for future gene therapy for the syndrome. By its very nature however this must be decades away.