More than 50 years ago, Jérôme Lejeune, a French geneticist discovered that people with Down syndrome have an extra copy of chromosome 21. It still remains a mystery why it results in impaired cognitive and physical development.
Researchers at the Sanford-Burnham Medical Research Institute thought they had found a clue. In a laboratory experiment conducted by scientists investigating Alzheimer’s disease, they found that mice with Down Syndrome with many of the same memory and learning impairment lacked the SNX27 protein just like the human brain of people with the syndrome.
Although chromosome 21 is not directly involved in the production of SNX27, it encodes a regular called miR-155 that inhibits the production. High levels of miR-155 in the brains of people with Down syndrome correlate with the less SNX27, according to a study published in Nature Medicine journal.
SNX27 protein keeps certain receptors on the surface of the cell necessary for the neurons to fire properly; so senior author Huaxi Xu believed the lack of SNX27 is partly to blame for the cognitive and developmental defects. Researchers are now investigating the molecules that might increase the production of SNX27 in the human brain.
Researchers and scientists have explored the possibility of using a noninfectious virus to introduce new SNX27 protein in the brains of mice with Down syndrome and found that the level of SNX27 goes back to normal after treatment and memory deficit is repaired. They are now looking into screening small molecules that might increase the production of SNX27.
Down syndrome affects approximately 6 million people worldwide, which can cause heart defects or early dementia. People with Down syndrome have either three full or partial copies of chromosome 21 instead of two found in the general population. This extra chromosome plays the key role in the relationship between Down syndrome and Alzheimer’s disease.
Just recently, scientists and researchers have located several genes and unique property on chromosome 21 that contribute to the increased risk of Alzheimer’s disease, which makes this a specific concern for people with Down syndrome.
Although people with Down syndrome are at risk, and it increases with each decade of life, many adults will not manifest the changes of Alzheimer’s disease in their lifetime.
Today, researchers at the University of Massachusetts Medical School found a way to turn off this extra chromosome so that it does not function and cause health problems. They call it chromosome therapy with the use of genetic engineering.
While this is somewhat a futuristic idea, lead researcher on the Nature paper said that this was the first time a single gene has been used to correct a chromosomal abnormality. This may seem long-term prospects, but this will accelerate a new strategy to help identify drugs that mimic the effects of turning off the extra chromosome in human cells.
Dr Laurence and her team found a way to reuse the XIST gene that affects the X chromosome to turn off chromosome 21. This has been tested in female mammals to ratchet down one of the X chromosomes. While it does not work in full human bodies, researchers have begun work to test this idea in mouse models.
Dr Laurence believed that this is an important tool to help them figure out what goes wrong in the cells of different organs and looks for drugs to treat them. Ultimately, this could lead to methods to turn off the extra chromosome in children with Down syndrome, or even before they are born.
Presently, researchers are hopeful they could find a way to turn off that extra copy of chromosome 21 causing Down syndrome, although this is clearly a long-term prospect.
Written by: Janet Grace Ortigas