ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Nature, Vol. 560, p. 291, 10 August 2018

For the first time, a drug based on the mechanism gene-silencing through RNA interference (RNAi) has received regulatory approval. We can expect that this is a forerunner of a new class of drugs targeting disease-causing genes.

It has been known for 20 years that short RNA molecules can attach to messenger RNA that carries a gene’s message and disrupt its translation to protein. This advance won Andrew Fire and Craig Mello the Nobel Prize, but efforts to turn it into medicine quickly hit hurdles. Scientists struggled to keep the fragile RNA molecules intact and direct them to the right tissue. The method was tried for hereditary transthyretin amyloidosis, where mutated forms of the protein transthyretin accumulate and sometimes impair heart and nerve function. Initially it did not work, but a more potent formulation worked in human trials; in a clinical trial in 225 people with hereditary transthyretin amyloidosis who showed signs of nerve damage, average walking speed significantly improved in those who received the treatment. This became the intravenous drug Patisiran, which was approved by the U.S. and E.U. regulators this year.

Many RNAi researchers are now working on a newer delivery method: attach chemically stabilized RNA onto a sugar molecule that homes in on the liver, the eye and central nervous system, or the heart.