Gene ZSCAN4 may help treat Down syndrome

Aug 31 2015

For people with Down syndrome, news from Elixirgen, LLC may brighten their day. The biotechnology company, located in the Science + Technology Park at Johns Hopkins, has outlined one of the best potential therapies yet for people with Down syndrome and other chromosome disorders in a paper entitled, "Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures," published in the journal DNA Research. Elixirgen plans to develop this technology into a treatment for the many complications that affect people with Down syndrome and other chromosome disorders at all age levels.

The paper demonstrates the use of the gene ZSCAN4 as a means to cure chromosome abnormalities. First, the company's researchers developed footprint-free ways to deliver ZSCAN4 into cells; the gene is expressed in a transient manner. Next, they found that such "hit-and-run" application of the gene significantly increased the proportion of cells with a normal number of chromosomes - also known as euploidy - in a population of mouse embryonic stem cells with mostly abnormal numbers of chromosomes - also known as aneuploidy. Finally, the researchers used the human version of the same gene on cells from people with Down syndrome and Edwards syndrome and found a significant increase in the number of euploid cells. Because Down syndrome and Edwards syndrome are caused by having three copies of a chromosome (21 and 18 respectively), the euploid cells no longer have the characteristics of either of those syndromes. Interestingly, ZSCAN4 is found ordinarily in the 2-cell stage of mammalian embryos and occasionally in stem cells, making the gene a natural chromosome therapy.

People with Down syndrome often experience a range of complications such as congenital heart defects, blood disorders and cognitive impairment. These complications can be less severe in people with mosaic Down syndrome - a form of Down syndrome where the person has a mixture of euploid and aneuploid cells instead of all aneuploid cells.

"Our goal is to alleviate the complications in people with Down syndrome by using ZSCAN4 therapy to increase their numbers of euploid cells," says Dr. Minoru Ko, Elixirgen's Chief Scientific Officer.

The company is currently focusing on bringing the Down syndrome therapy into the clinic. However, because there are many other chromosome disorders that are without a sufficient treatment, their discovery of aneuploidy correction may offer a lead to more cures in the future.