TSRI Comes Up With Compound That is Beneficial for Huntington's Disease Mice and Their Offspring

by Dr. Trupti Shirole on Dec 24 2014 8:40 PM

 TSRI Comes Up With Compound That is Beneficial for Huntington
A new study by scientists at The Scripps Research Institute (TSRI) suggests that drug compounds which benefit parents can also cause changes in genetic expression that benefit offspring. Mice studies reveal that the offspring of mice treated with a drug had delayed onset and reduced symptoms of Huntington's disease, an inherited, degenerative disease that causes a loss of motor skills, cognitive impairment and death.   
Lead author of the study said, "Although there is a test to see if a person will develop Huntington's, many people don't get tested because there are no good treatments to prevent or reduce symptoms. One exciting aspect of our study is that the parental drug treatment made the offspring better, not worse, like other compounds known to cause transgenerational effects.”

Epigenetic changes are changes in gene expression triggered by diet or toxins in the environment without changing the genetic sequence. DNA methylation, a process where a methyl group is attached to DNA, often leads to epigenetic changes silencing gene expression.

TSRI researchers tested compounds called histone deacetylase (HDAC) inhibitors to see if they can induce epigenetic changes to help lessen the severity of diseases such as Huntington's in the next generation.

In the first part of the experiment, while testing the effects of HDACi 4b on gene expression in mice brain and muscle samples, it was found that HDACi 4b changed the expression of genes related to DNA methylation. They also showed that HDACi 4b treatment of human patient fibroblast cells altered DNA methylation of more genes on the male-carried Y chromosome than other chromosomes.

Thereafter researchers administered HDACi 4b to a group of male mice with a human Huntington's disease gene, while another group of mice did not receive treatment with the compound. One month later, the mice were bred, and their offspring were tested for symptoms of the disease.

The female offspring from the drug-treated mice showed no differences, but the male mice showed a delay in disease onset and a reduction of motor and cognitive symptoms that included improved performance in tests of balance, speed and memory.

Researchers are now curious to understand whether the effects of HDAC inhibitors could be passed down through the female germline, and whether the beneficial effects could persist in generations of grandchildren or great-grandchildren.

The study will appear in the journal ‘Proceedings of the National Academy of Sciences’.


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