Innovations in Down Syndrome Research
Research Overview
Down syndrome is an inherited genetic condition caused by an extra copy of chromosome 21. There are more than 350,000 individuals with Down syndrome in the United States alone. With an incidence of 1 in 800 live births, it's the most common form of inherited intellectual disability. Many medical conditions associated with Down syndrome can now be successfully treated. As a result, Down syndrome individuals have a much longer life expectancy. However, no therapies have been approved to address intellectual disability in this population.
Our research on a mouse model of Down syndrome has revealed why brain circuits with three copies of genes from human chromosome 21 have a reduced capacity to learn. Based on this research, we have developed a drug therapy that improves learning in these animals.
Now there is hope that these findings can be quickly translated into useful therapies to improve cognitive abilities in people with Down syndrome.
We need your financial help to bring these findings from the lab to the clinic. For more information on how you can support our research please visit Make a Gift.
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More Research Details
Individuals with Down syndrome have an extra copy of more than 200 genes. The extra copy of these genes disrupts the delicate balance of proteins and molecules in the body. For the brain this means that it cannot function normally, causing reduced learning and memory abilities.
Scientists have created mice that carry an extra copy of many of the genes triplicated in Down syndrome. These mice possess fundamental features of Down syndrome such as deficits in learning and permit exploration of potential treatment strategies. Researchers at Stanford and elsewhere have discovered some potential causes of memory deficits in this mouse model of Down syndrome.
Studies in the Garner lab have confirmed that in this mouse model of Down syndrome communication between two types of brain cells—excitatory and inhibitory neurons—is out of balance. There is too much inhibitory communication, which prevents learning from properly taking place. It’s as if somebody forgot to release the parking break—the car just won’t go.
The Garner lab further investigated whether inhibitory communication between neurons could somehow be reduced in this mouse model. For this purpose, Down syndrome mice and normal mice were tested on two tasks that were designed to assess learning and memory. As expected, the Down syndrome mice performed significantly worse than the normal mice.
The Down syndrome mice were then treated for several weeks with different drugs, which are known to reduce inhibitory communication. These drugs work by partially blocking a receptor located on the neurons called GABA A receptor. Blocking these receptors should reduce inhibitory communication, thereby increasing excitatory communication. When tested on the learning and memory tasks, the Down syndrome mice now performed almost as well as the normal mice. Even several weeks after drug treatment had been terminated, these mice still performed better.
These results confirm that too much inhibitory communication between neurons indeed prevents learning from taking place in this mouse model of Down syndrome. Reducing this inhibition with specific drugs restores the balance between inhibitory and excitatory neurons so that learning can take place.
The results also suggest that a similar treatment strategy may be able to address the cognitive deficits seen in individuals with Down syndrome. Several known drugs can turn down inhibition through GABA A receptors. Some of the drugs used in the animal studies have a long history of safe use in humans, but they have not been used to treat individuals with Down syndrome.
We are now planning a clinical trial to confirm that this treatment is safe and effective in humans with Down syndrome. The trial will begin soon, but is dependent on successful fundraising. Through the efforts of motivated doctors and scientists —and your help—there is real hope for improvement of cognitive function in individuals with Down syndrome.
For more information on how to support our research, please visit our Make a Gift page.
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