Triplet Therapeutics launches with $59 million to develop antisense therapies for Huntington’s and more

Huntington’s disease is one of more than 40 diseases known to be caused by a genetic glitch in which a trio of nucleotides—CAG in Huntington’s—is erroneously repeated. It’s as if someone using the genetic equivalent of a word processor copied the sequence and then repeatedly pasted it: CAGCAGCAGCAG.

Longer repeats are associated with earlier onset of the disease. A start-up called Triplet Therapeutics now says it has discovered a way to prevent the repeats from expanding to dangerous levels in the first place.

The company last month announced a $10 million seed investment from Atlas Venture and $49 million in series A financing led by MPM Capital and Pfizer Ventures.

Triplet CEO Nessan Bermingham says three recent studies—for myotonic dystrophy, spinocerebellar ataxias, and Huntington’s disease—all point to genetic variants in the DNA damage response (DDR) pathway as the culprits for accelerating the development of these triplet-repeat disorders.

Under normal circumstances the DDR is our friend, instructing a large number of proteins to coordinate maintenance and repair of our genome. But during transcription, DDR proteins can get confused by the redundant triplet-repeat sequences and mistakenly increase the number of triplet repeats.

“The repeats drive the disease, but not the repeats you are born with,” Bermingham says.

Triplet is developing antisense oligonucleotide and RNA interference drugs that decrease the expression of certain DDR proteins. The firm says testing in mice shows that reducing levels of the DDR proteins halts triplet-repeat expansion. If the strategy is successful, just a handful of drugs could stall the progression of more than 40 conditions that geneticists classify as triplet-repeat diseases.