Male offspring from the drug-treated mice in the study showed a delay in disease onset and a reduction of motor and cognitive symptoms.
Any stimulus that can be detected outside the body has the potential to cause epigenetic modifications.
If you consider a DNA sequence as the text of an instruction guide that describes how to create a human body, epigenetics is as if someone has taken a pack of highlighters and used various colors to mark up particular parts of the text in different ways.
For example, someone might use a yellow highlighter to mark parts of the text that are important and an orange highlighter to mark parts that are not as important.
Evidence has shown that changes in gene expression can be triggered due to environmental factors, such as stress levels, smoking, habit, lifestyle and even finances.
While the genetic sequence remains unchanged, epigenetic changes can be passed to the next generation and have been linked to conditions such as obesity and autism-related disorders. Epigenetic changes are often caused by DNA methylation, a process whereby a methyl group is attached to DNA, silencing gene expression.
Research suggests that a small percentage of our epigenetic tags cling on. And potentially our worst habits - smoking or overeating - are the ones that can be passed on to offspring and even further down the hereditary line.
To test whether therapies can change gene expression in parents to help their offspring, scientists tested Huntington's disease-afflicted mice.
It is estimated by the Huntington's Disease Society of America that over a quarter of a million Americans either have Huntington's disease or are at risk of inheriting the degenerative disease from a parent.
Memory and motor skills of offspring improved by drug compound
The authors of the study say this is the first time scientists have shown that drug compounds that benefit parents can also cause changes in genetic expression that benefit offspring - in this case, improved memory and motor skills.
Elizabeth Thomas, associate professor at The Scripps Research Institute (TSRI), who led the study, comments:
"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."
Thomas has studied Huntington's disease for 15 years, after learning that a close friend's mother was suffering from the disease.
"If your mom or dad carries the mutation, you have a 50-50 chance of inheriting the disease," says Thomas. "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."
Thomas and colleagues have 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 previous studies, the same investigators determined that the compound HDACi 4b worked to reduce symptoms and delay disease onset in mice. The researchers were curious as to whether these benefits could be passed on to offspring through epigenetics.
Authors of the new study include TSRI's Associate Professor Elizabeth Thomas and Professional Scientific Collaborator Jia Haiqun.
Image credit: TSRI
The researchers tested the effects of HDACi 4b on gene expression in mouse brain and muscle samples, and they found:
- HDACi 4b changed the expression of genes related to DNA methylation
- HDACi 4b treatment of human patient fibroblast cells altered DNA methylation of more genes on the male-carried Y chromosome than other chromosomes.
The compound was administered to a group of male mice with a human Huntington's disease gene and compared with a similar group of mice that did not receive the compound. After 1 month of treatment, the mice were bred, and their offspring were tested for symptoms of the disease:
- Female offspring showed no differences
- Male offspring from the drug-treated 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.
The study concludes that offspring of mice treated with the drug have a delayed onset and reduced symptoms of Huntington's disease.
Future investigation will examine 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.
Another focus of their ongoing research is the effects of other types of HDAC inhibitors already approved to treat certain cancers and bipolar disorder. "Many patients with these diseases have kids, so a big question is how these treatments might affect their offspring," states Thomas.
The findings of this study are reported ahead of print in this week's Early Edition of the journal Proceedings of the National Academy of Sciences.
Medical News Today recently reported that researchers have discovered that a gene called "huntingtin" plays an important role in long-term memory.