Disabling the "sonic hedgehog" helped mice with Down syndrome
Researchers at Johns Hopkins University and the US National Institutes of Health, working under the guidance of Professor Roger Reeves, have identified a compound whose single intake immediately after birth significantly improves the learning ability and memory of a mouse model of Down syndrome.
Down syndrome is a rare genetic disease in which the human genome contains three copies of the 21st chromosome and, accordingly, 3 copies of more than 300 genes localized on it. Down syndrome is manifested by mental retardation, characteristic facial features, a decrease in life expectancy, as well as, in some cases, problems with the heart and other organs. Given the number of genes involved in the disease, the emergence of effective methods of its treatment is almost unrealistic.
In their study, the authors used genetically modified mice with additional copies of 50% of the genes localized on the 21st human chromosome. Animals were characterized by many characteristics of the disease, including a relatively small cerebellum (in people with Down syndrome, the size of the cerebellum is about 60% of the norm) and difficulties with memorization and learning.
Based on the results of earlier experiments devoted to the study of the mechanisms of the influence of Down syndrome on brain development, the authors attempted to stimulate a biochemical cascade known as a signaling mechanism that triggers the growth and development of the brain, mediated by the sonic hedgehog protein ("sonic hedgehog" – the gene of this protein is named after the hero of the computer game of the same name). To do this, they once injected newborn mice with a compound that is an agonist of this protein. This was enough to form a full-fledged cerebellum in animals.
The cerebellum of a mouse model of Down syndrome after therapy with an experimental drug (left),
without therapy (in the center) and the cerebellum of a normal mouse (on the right). Figure from the article in Sci. Transl. Med.
Moreover, when performing standard tasks used to assess the ability of mice to memorize and learn, such as a water maze, the animals that underwent therapy were not inferior to normal mice.
According to Reeves, additional research is needed to find out the reasons for the effectiveness of such treatment. The fact is that the analysis of hippocampal cells, considered responsible for learning and suffering from Down syndrome, did not reveal any changes, presumably caused by experimental therapy. According to one hypothesis, the positive effect of therapy is due to an increased relationship between the cerebellum and the hippocampus.
The creation of a drug suitable for clinical use on the basis of an experimental drug is very problematic, since exposure to an extremely important biological mechanism is fraught with many undesirable side reactions, including an increased risk of cancer. However, the results of the study may form the basis of a more selectively acting therapy. On the other hand, it is obvious that such therapy will not be able to provide a complete cure for this extremely complex disease.
Article by Ishita Das et al. Hedgehog Agonist Therapy Corrects Structural and Cognitive Deficits in a Down Syndrome Mouse Model published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Johns Hopkins Medicine:
Experimental Compound Reverses Down Syndrome-Like Learning Deficits in Mice.
05.09.2013