Startup Constellation Pharmaceuticals aims to develop drugs that target a broad array of diseases by manipulating one of the fundamental mechanisms by which cells control the expression of genes: epigenetics. By designing compounds to alter the activity of the enzymes that coil and unwrap the genome, Constellation hopes to turn off errant genes and turn on ones key to fighting disease.
“Epigenetics is the mechanism that allows genes to be expressed in the right spatial and temporal manner, so it’s just as important as genetics,” says Yang Shi, a Harvard Medical School pathology professor, who founded Constellation along with David Allis of Rockefeller University and Danny Reinberg, of New York University. “Our first line of attack will be on enzymes that either write or erase modifications.”
Constellation announced last week that it has completed its second round of financing, raising $22 million, for a total of $54 million; confirming its own promise and the potential for epigenetic drugs. The new investment comes from Third Rock Ventures, which helped launch the Cambridge, MA, company two years ago, and the venture capital arm of pharmaceutical giant GlaxoSmithKline, among others.
Epigenetics refers to changes in cell traits or characteristics that are inherited without changes in DNA sequence. Epigenetic regulation is most commonly controlled by a number of chemical modifications that alter the way DNA is packed, which in turn makes those genes easier to turn on or off. This natural pattern of activation, which is influenced by fetal environment, stress, diet, exercise and toxic exposure, among other things, is unique to each person. This regulation can go awry in the development of disease. Identical twins can have different patterns of epigenetic modifications, helping to explain why one twin can develop cancer despite similar environmental exposures.
Developing drugs to reverse these mistakes cell has become a hot target over the last few years as scientists learn more about the key role these mechanisms play in variety of diseases, including neurological and metabolic diseases, such as Alzheimer’s and diabetes.