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New drug could improve the learning ability of individuals with Down syndrome

Date: 6.7.2010 

Researchers from Texas might be able to help the children with Down syndrom some day. They found out, that there may be a protein responsible for the impairment of cognitive functions. This protein belongs to amyloids, which are pathological protein aggregates with specific properties. Abnormal accumulation of amyloid leads to many diseases. In this study the scientists used mice with a genetical mutation which led to the genesis of a condition similar to Down syndrome. They found out, how to reduce the level of the amyloid protein in the brain.

The reduction of the level of the amyloid protein in the brains of mutant mice suffering from a disease similar to Down syndrome improves their learning ability. This study was performed by a group of researchers at the UT Southwestern Medical Center and it was published in the online journal PLoS One.

"This preliminary study on animal models opens up an interesting possibility that drugs that are able to lower the levels of the amyloid beta protein may be of some benefit to children with Down syndrome," said Craig Powell, who led the study.

The origin of Down syndrome is the presence of an extra copy of chromosome 21, so that the disease is also known as trisomy 21. Indeed, on this chromosome there are situated genes that are responsible for the synthesis of the protein beta amyloid.beta-amyloid

Individuals with Down syndrome have a higher level of this protein in their brain, although it is not sure that it contributes to the lack of intellectual ability. "Anyway, from late adulthood, the majority of these patients show early signs of Alzheimer's disease," observed Powell. Alzheimer´s disease is the most common form of dementia. The amyloid protein plays an important role in the pathophysiology of this disease.

For their study the researchers have used mice with a genetic anomaly that reminds the human Down syndrome: these mice have three copies of a number of genes - including those related to the beta amyloid protein - and show significant learning difficulties, which was valued with a series of standard tests, such as the test for the ability of orientation in a labyrinth.

The researchers fed these genetically altered mice for four months with an experimental drug called DAPT, which is able to block gamma-secretase, an enzyme essential for the production of the amyloid beta protein.

Already four days of treatment could reduce by 40% the brain levels of the beta amyloid protein, leading to a gradual improvement in performance of rodents, some of which have managed to reach a speed of learning comparable to that of normal mice.

Powell warns, however, that the blocked enzyme is involved in many other brain functions, not only in the control of the beta amyloid protein, and that this current gamma-secretase inhibitors may have undesirable side effects. "Our goal now is to identify drugs that block the ability of this enzyme to produce the amyloid protein without interfering with its ability to perform other functions," says Powell.

Translated by Pavla Čermáková




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