Man made molecules may be the key to fighting against Huntington's disease and a similar disease known as Machado-Joseph disease by interrupting the translation of the mutant copy of the gene that causes these two neurological diseases.
The two fatal inherited diseases, Hunting's and Machado-Joseph are caused by abnormal repeats of a segment in a person's DNA represented by CAG this then results in the consequent production of malfunctioning proteins which then cause the two diseases. A person that is a carrier of the disease contains one normal copy of the gene and also a mutated copy. This means that the more the mutated gene is replicated the more severe the disease is and the earlier it appears in life. In Huntington's disease the replication of CAG occurs in the Hunting gene and in the other disease in occurs in the ataxin-3 gene. While the mutated version of the gene is known for its fatal and terrible disease, the normal version of the gene is important for embryonic development, nerve function and other processes. This makes it even more precise to treat the mutant gene as the treatment must not interfere with the normal gene.
"Attempting to intervene is very risky, but because the problem is important, it's worth doing," Dr. David Corey professor of pharmacology and biochemistry at UT Southwestern and senior author of the study. So far researches in the lab have been able to create short lengths of molecules similar to RNA, these are known as PNA and LNA and also short lengths of RNA called siRNA. These have been specially designed to bind to CAG repeats, which prevent the cells from creating abnormal proteins. These have been tested on human cells from patients with these diseases, in the case of a cell with Huntington's disease PNA, LNA and siRNA were able to decrease the amount of mutant proteins that were produced, even up to 100 percent.
However the effectiveness of the PNA, LNA and siRNA differed among different patient’s cells, while some worked well against the mutant gene, some however also affected the normal gene and even minimizing the production of proteins in both genes. However this indicates that with further study into these molecules in order to be only effective on the mutant gene without affecting the normal gene. "It is encouraging that small chemical changes could substantially enhance selectivity," "If we can test a handful of compounds and identify better ones, we have reason to believe that more testing will continue to produce significant improvement." Dr. David Corey. To date these molecules have only be experimented with cultured cells, however further studies plan to use these molecules on animals. This may be the key to treating fatal diseases such as Huntington's disease.
Reference:
http://www.sciencedaily.com/releases/2009/05/090503132623.htm (Article)
http://www.sciencedaily.com/releases/2007/04/070422141755.htm (Photo)
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