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December 19, 2009

Epigenetic therapy

Epigenetics research takes aim at cancer, Alzheimer's, autism, other illnesses.

Two mice. One weighs 20 grams and has brown fur. The other is a hefty 60 grams with yellow fur and is prone to diabetes and cancer. They're identical twins, with identical DNA. Their varying traits are controlled by a mediator between nature and nurture known as epigenetics. A group of molecules that sit atop our DNA, the epigenome (which means "above the genome") tells genes when to turn on and off.

The mother of the brown, thin mouse was given a dietary supplement of folic acid, vitamin B12 and other nutrients while pregnant, and the mother of the obese mouse was not. (Though the mice had different mothers, they're genetically identical as a result of inbreeding.) The supplement "turned off" the agouti gene, which gives mice yellow coats and insatiable appetites.

Last year, the National Institutes of Health announced that it would invest $190 million to accelerate epigenetic research. The list of illnesses to be studied in the resulting grants reveals the scope of the emerging field: cancer, Alzheimer's disease, autism, bipolar disorder, schizophrenia, asthma, kidney disease, glaucoma, muscular dystrophy and more.




Methylation-modifying drugs might be a new avenue for treatments. He also hopes that his findings will provide a new tool for doctors to diagnose autism.

"Methylation has been very hot in the cancer field for a number of years," Gregory says. "To find something like this associated with autism is very exciting."

Epigenetic therapy is still very inexact -- "a pretty broad brush," says Jirtle. But oncologists have seen some success in using it against leukemia. Azacitidine, sold as Vidaza and used to treat bone-marrow cancer and blood disorders, became the first FDA-approved epigenetic drug in 2004. When tumor-suppressing genes aren't doing their job, due to a genetic mutation or hypermethylation, cancer cells can replicate uncontrollably. But by manipulating the epigenetic marks, doctors can get tumor-suppressing genes to work again. Toxicologists also have a big stake in epigenetics. A 2005 study by Washington State University molecular biologist Michael Skinner generated buzz with his finding that when a pregnant rat was exposed to high doses of pesticides, her offspring plus the next three generations suffered from high rates of infertility. (Some scientists have challenged Skinner's work because they have not been able to reproduce his results in their labs.)

The potential human implications -- do the chemicals we ingest today affect our great-grandchildren? -- are tremendous. In addition to pesticides, toxicologists are studying chemicals in plastics, such as phthalates and bisphenol A, to see if they could enhance our risk of disease by altering the epigenome.



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