Researchers Develop Method to Potentially Eliminate Down Syndrome

A team of researchers from Mie University in Japan has made significant progress in the potential treatment of Down syndrome by successfully deleting an extra copy of chromosome 21 in lab-grown cells. This achievement could change the landscape of treatment for the condition, which affects approximately one in 700 births in the United States, with around 250,000 individuals currently living with it.

Down syndrome arises when a person has three copies of chromosome 21 instead of the usual two. This genetic variation affects brain development and can lead to various intellectual disabilities and health challenges. The researchers utilized the CRISPR-Cas9 gene-editing technology, often described as ‘molecular scissors,’ to accurately remove the extra chromosome, ensuring the integrity of the remaining parental chromosomes.

Advancements in Gene Editing

The scientists demonstrated that their CRISPR-Cas9 system could distinguish the extra chromosome from the two original copies inherited from each parent. Following the editing process, the corrected cells exhibited more typical gene activity and cellular behaviors, particularly in areas associated with brain development.

Despite this promising proof of concept, experts emphasize that the research is still in its early stages and far from being a viable treatment. Dr. Roger Reeves from Johns Hopkins University School of Medicine highlighted that while the removal of an extra chromosome has been achievable for over a decade, applying this technique to a living organism poses immense challenges. He noted, “A human body contains trillions of cells, each carrying the extra chromosome, so there is currently no realistic way to apply this as a treatment.”

The complexity of the human body makes it difficult to replicate the success achieved in lab-grown cells. Researchers have struggled to identify which specific genes on chromosome 21 contribute to the various traits and health issues observed in individuals with Down syndrome. The variability in genetic backgrounds among individuals complicates the search for consistent genetic signatures that could be targeted in therapy.

Challenges Ahead

Currently, there is no cure for Down syndrome. Most existing research focuses on managing symptoms or addressing related health conditions, such as heart defects or learning difficulties. In contrast, the Japanese scientists’ approach directly targets the root cause of the disorder by aiming to eliminate the extra chromosome.

The methodology involved testing two types of lab-grown cells: induced pluripotent stem cells reprogrammed from adult tissue and skin fibroblasts. By employing CRISPR-Cas9 to create breaks at multiple sites on the extra chromosome 21, the team encouraged the cells to eliminate the duplicated chromosome entirely. To enhance the likelihood of success, they suppressed the cells’ DNA repair mechanisms, which typically work to mend broken DNA.

Despite these advancements, only a small fraction of the tested cells successfully lost the extra chromosome. Dr. Reeves explained the scale of the challenge: “Theoretically, more than 800 million cells would need to have the extra chromosome 21 removed to create a ‘typical’ person.” The current inability to target every cell, combined with the risk of cell death, renders this approach impractical for application in living infants.

While the research highlights the potential of CRISPR technology, the team acknowledges significant hurdles to overcome. Major challenges include delivering the CRISPR edits accurately to the appropriate cells in the body, preventing unintended DNA damage, and ensuring safety in embryos or living individuals. Ethical considerations also complicate the use of gene-editing tools on human embryos, with many countries currently banning such practices due to concerns about unintended consequences and the possibility of creating ‘designer babies.’

Nevertheless, researchers view this work as a crucial milestone. It demonstrates that CRISPR can effectively eliminate an entire chromosome, paving the way for new avenues of research into Down syndrome at the cellular level and potentially guiding future therapeutic interventions.