Epigenetics revolution

Research could lead to a breakthrough in the fight against cancer, disease

Putting aside discussion about parents passing experiences to their offspring, the biggest gain in studying epigenetics may actually lie in ordinary human diseases.

The epigenetic changes that happen within our own bodies as we age can cause disease.

The big one is cancer. Of the enzymes in our cells that relate to epigenetic activity, David Picketts of the Ottawa Hospital Research Institute estimates that about 500 are somehow related to various cancers.

Researchers hope that if unwanted coatings can be added to your DNA as you age, maybe they can also be stripped away again with drugs.

Just like cleaning rust off an old garden tool.

“A lot of epigenetics is somewhat reversible. If we can find out what went wrong we can maybe try to reverse that,” Picketts said.

In theory, some epigenetic changes that cause disease could be reversed with drugs that strip the DNA back to its original condition.

As far back as 2004, a California team proposed doing this in a paper called ‘Epigenetics in human disease and prospects for epigenetic therapy.’ They looked forward to work that would inhibit — or block — the little molecules that have attached to a person’s DNA, and let genes do their proper jobs again.

“Inhibitors of DNA methylation rapidly reactivate the expression of genes that have undergone epigenetic silencing, particularly if this silencing has occurred in a pathological situation,” they wrote in the journal Nature.

The practical work is now underway. In 2016, a team headed by Johns Hopkins University began Phase 2 clinical trials for a drug to do epigenetic therapy in people with colorectal cancer. This means they have had success in test tubes and lab animals, and have moved on to human tests.

The teams announced that the drug “corrects errors in methylation, a common epigenetic process that determines whether a gene is switched on or off. Genes that are inappropriately switched off do not produce proteins needed for normal function and can contribute to diseases such as cancer.”

The hope is to make a standard colon cancer drug effective for a larger number of people, the team says, by stripping away the methyl groups that are responsible for making some patients “desensitized” to the drug.

Meanwhile researchers in other fields are exploring parallel work.

The American Gastroenterological Association announced in 2015 that “epigenetics represents an important, potentially reversible, target for IBD treatments.” IBD is inflammatory bowel disease.

The hope is that understanding one person’s individual genetic changes will lead to individual treatment.

It means that two tumours that look on the outside like the same type would need different treatment — one to combat the action of enzyme A and a different one for a genetic change caused by enzyme B.

The U.S. National Institutes of Health summarize the problem this way: “Certain genes normally work to protect against cancer. Some epigenetic marks can turn these genes off, increasing the risk of cancer. Scientists still do not fully understand why certain epigenetic marks switch off the genes we need to stay healthy, or turn on genes that lead to disease.”

Epigenetic changes are a natural part of aging, the NIH says, but “this buildup may also increase the likelihood that certain genes will be changed in a way that leads a person to develop age-related diseases, such as cancer and diabetes.”

Disease caused at least partly by epigenetic changes include various cancers, obesity, heart disease and less common health problems, such as Fragile X syndrome, Angelman syndrome and Prader-Willi syndrome.

If we can find out what went wrong we can maybe try to reverse that.