Researchers Pioneer Technique to Remove Extra Chromosome in Down Syndrome

A team of researchers from Mie University in Japan has made significant strides in the potential treatment of Down syndrome, successfully deleting an extra chromosome in lab-grown cells. This breakthrough could reshape how the condition, which occurs in approximately one in 700 births globally, is understood and treated.

Down syndrome is characterized by the presence of three copies of chromosome 21, which alters brain development and can lead to various challenges, including intellectual disabilities and learning difficulties. Currently, an estimated 250,000 individuals in the United States live with this condition.

Using a state-of-the-art DNA-editing tool known as CRISPR-Cas9, often referred to as “molecular scissors,” the researchers were able to precisely cut away the surplus chromosome from the cells. This innovative method distinguished the duplicated chromosome from the two original parental copies, thereby ensuring that the cells retained one chromosome from each parent.

Promising Results from Laboratory Testing

In their experiments, the team observed that the edited cells began to exhibit more typical patterns of gene activity and cellular behavior, particularly in pathways associated with brain development. While these results are promising, experts caution that the journey from laboratory success to practical treatment remains a long and complex one.

Dr. Roger Reeves, a professor at Johns Hopkins University School of Medicine, emphasized that while removing an extra chromosome from a single cell has been feasible for over a decade, scaling this process for an entire human body presents immense challenges. “A human body contains trillions of cells, each carrying the extra chromosome,” he explained. “Right now, there is no realistic way to apply this as a treatment.”

Most existing research on Down syndrome focuses primarily on managing symptoms rather than addressing the genetic root causes. Techniques such as fetal surgery can sometimes correct heart defects prior to birth, while postnatal therapies often concentrate on learning challenges and other medical complications.

Technical and Ethical Challenges Ahead

The Japanese research team acknowledges several obstacles that need to be addressed before their technique could be considered a viable treatment option. Key challenges include delivering CRISPR edits to the appropriate cells in the body, avoiding unintended DNA damage, and ensuring that any interventions are safe for embryos or living individuals.

Despite the technical hurdles, researchers remain optimistic. The team conducted their study using two types of lab-grown cells: induced pluripotent stem cells, which are reprogrammed from adult tissue, and skin fibroblasts. By applying CRISPR-Cas9 to cut multiple sites on the extra chromosome 21, they induced the cells to eliminate the duplicated chromosome entirely.

To enhance the likelihood of success, the researchers suppressed the cell’s DNA repair mechanisms, which typically work to mend broken DNA. This strategic move increased the chances that the entire extra chromosome would be discarded rather than repaired.

While only a small fraction of the cells tested successfully lost the extra chromosome, the implications of this research could be far-reaching. Dr. Reeves noted that theoretically, over 800 million cells would need to have the extra chromosome removed to create a “typical” individual, highlighting the scale of the challenge.

The ethical implications of gene editing in humans are another significant factor. The use of CRISPR on human embryos has sparked considerable debate and is currently banned in many countries due to concerns about unintended consequences and the broader implications of creating “designer babies.”

The work conducted by the Japanese team marks a crucial milestone in genetic research, demonstrating the capability of CRISPR to eliminate an entire chromosome. This achievement not only opens new avenues for studying Down syndrome at a cellular level but may also inform future therapeutic strategies. As research continues, the hope is that it will lead to more effective interventions for individuals living with this condition.