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Possible Treatment for Down's Syndrome Retardation may Involve Interference with Gene - Same Gene might Cause Alzheimer's

July 6th 2006

Possible Treatment for Down's Syndrome Retardation may Involve Interference with Gene - Same Gene might Cause Alzheimer's

Health

Stanford University researchers believe they may be able to “reverse the cognitive decline” that frequently affects those with Down’s syndrome in middle age.  "We may now have the opportunity to make a big difference in people's lives," according to neurologist William Mobley, MD, PhD. "If we can decrease the expression of this gene we may be able to provide something more than supportive care to people with Down syndrome."

Mobley and his team believe they have found the gene that when overexpressed, causes neurons responsible for attention and memory to shrivel and stop functioning normally.  It may be possible to “interfere” with the gene.

Down’s syndrome is the leading cause of mental retardation in the United States.  There are more than 300,000 people nationwide have Down syndrome, which is caused by an extra copy of chromosome 21, giving them a total of three.  Up until now, there has been little molecular or Neurological research done on the subject.

 

There are many symptoms associated with the disorder.  "Down syndrome results in an extraordinarily complex constellation of symptoms," said lead author and senior research scientist Ahmad Salehi, MD, PhD. "We've done what many people thought was impossible: We've dissected it genetically to correlate one of the most troubling symptoms - cognitive dysfunction - with one particular gene. While it's not the only gene involved, its presence in three copies makes a significant difference."

The same gene that has been identified with the early-onset Alzheimer's disease, called App for amyloid precursor protein, is directly linked to degeneration of a specific group of neurons in the brains of those with Down syndrome.  This research confirms earlier research.  Neuronal degradation in people with Down syndrome is the result of an interrupted conversation between nerve cells in a specific part of the brain.

 

The researchers compare the problem with the classroom troublemaker.  They say the signaling neuron needs feedback to thrive.  The neuron lobs specialized compounds called neurotransmitters toward its neighbor and awaits a response to its molecular “spit wads”.  The target cells then fire back a set of molecules, or nerve growth factor (NGF).  The NGF is engulfed by the membrane of the instigator cell and is shuttled to the cell body in a process called retrograde transport. Once there it acts on the nucleus to stimulate the expression of genes that support neuronal growth. Interrupting this intercellular tit-for-tat causes the neuron to wither away. 

"First we need to figure out at a molecular level how App works in Down syndrome," said Mobley. "Then we need to examine other genes that might be involved and test possible compounds in mouse and human cells. If we are able to do all that, we might begin to think of helping children and adults with Down syndrome to develop and age more normally."

The research is published in the to July 6 issue of Neuron

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