New Findings Give Hope For Down's Syndrome Patients

Down’s syndrome is the most common chromosomal abnormality which leads to a mental condition associated with intellectual disabilities. Disease, also known as trisomy 21, is caused by additional copy of chromosome 21 present in all cells of the body of affected person.

Down’s syndrome severely affects mental and physical abilities

Down’s syndrome is usually associated with delays in mental development and physical growth, as well as characteristic and recognizable facial features. The IQ of the young individuals with Down’s syndrome is usually around 50, while the normal young adults have average IQ of 100. People with Down’s syndrome often demonstrate speech delays and delayed motor skills (problems with learning how to walk in childhood are very typical). They are also often affected by various heart conditions.

The symptoms of Down’s syndrome are associated with the presence of additional copies of genes coming from the third chromosome 21. This chromosome is one of the smallest in our cells and codes for approximately 200-250 genes. Excessive genetic material causes over-expression of certain genes and presence of excessive amounts of protein products of these genes. Excessive quantities of these proteins disrupt normal regulation of many biochemical processes and bodily functions.

The presence of additional genetic material can have different medical consequences and can damage various organs in the body. This results in significantly lower average life expectancy for people affected by this condition, which stands now at approximately 60 years. Towards the older age, people with Down’s syndrome tend to develop neurodegenerative diseases and suffer from dementia. Researchers have recently identified the genes that are responsible for clinical manifestations of Down’s syndrome and cause the biggest problems for people having this condition.

Gene therapy bring hope to people with Down’s syndrome

Genetic conditions like Down’s syndrome are hard to treat and impossible to cure at present time. Any attempts to cure must somehow address the problem of additional genetic material in the cells of affected individuals. However, the progress of gene therapy in recent years brings hope that our understanding of gene functioning on the level of whole body will eventually result in the development of genetic tools capable to address this problem. Now we are already able to activate or suppress certain genes in the body, and although most of this work is done on experimental animals, the development of appropriate and safe tools for manipulations with human genome is only a matter of time.

Till recently, the exact mechanism leading to learning disabilities and delay in physical growth in patients with Down’s syndrome was unknown. New findings announced by scientists from California and published in Nature Medicine seem to give answer to this question.

Genes Responsible For Mental Disability In Patients With Down’s Syndrome Are Now Identified

Molecular mechanisms behind the development of symptoms of Down’s syndrome are very complex 

Scientists researching this problem have found a connection between Down’s syndrome and a protein called SNX27 (sorting nexin 27). This protein regulates the level of specific receptor proteins called glutamate receptor on the surface membrane of nerve cells.

These receptors, like many other receptors in the brain, are involved in communication between the cells. A small molecule of neuromediator called glutamate transmits the nerve signal from one cell to another. Receptors detect this molecule and recognize it as a specific signal to which they respond in a specific and pre-programmed manner. If the level of glutamate receptors is decreased, the cross-talk between neurons becomes affected and eventually this results in impaired brain functions and mental disability. This is how the symptoms of Down’s syndrome develop.

In patients with Down’s syndrome, the level of protein SNX27 is significantly smaller than in people with normal brain functioning. Researchers checked which factors affect the level of this protein and how. They found that chromosome 21 carries a gene for a specific compound that decreases the synthesis of SNX27 in nerve cells. This compound exists in normal brain as well and its presence does not create any problems. The problem comes with the additional copy of chromosome 21. In the presence of excessive amount of genetic material, nerve cells produce excessive number of these inhibitory compound which results in the deficit of SNX27.

New discovery brings a possibility of functional cure for Down’s syndrome

Recent findings provide a clear picture of what’s going on in the brains of patients with Down’s syndrome. Understanding of these complicating molecular mechanisms also gives a hope for development of cure. Scientists have done experiment on mice with Down’s syndrome. They demonstrated that the level of protein SNX27 in the brain can be returned back to normal when they blocked the synthesis of inhibitory compound that affects the SNX27 level. The mice in their experiments regained normal behavior and cognitive functions.

Blocking of inhibitory molecules production was achieved in these experiments with the use of gene therapy. Similar approach suitable for humans is not yet developed. However, this research provides a clear blueprint for developing a similar approach to treat Down’s syndrome in people.

It remains to be seen how effective the newly discovered treatment for mice is and how long its effects last. But for the first time in history now we can have reasonable expectations that proper drugs for people with Down’s syndrome will be developed and the disease will be successfully treated.