For the first time, a medication that silences genes has won regulatory approval in the US. Not only is this a huge win for the amazing technology involved, it's also a treatment for a rare hereditary condition that causes nerve damage.
The drug, called patisiran, can now be used to treat hereditary transthyretin amyloidosis (hATTR) – where mutated proteins build up in the body, affecting crucial heart and nerve functions.
It's a major first, and a huge moment for RNA interference (RNAi): the technique of silencing genes by altering the messages that RNA (ribonucleic acid) molecules pass around the body, changing which proteins get produced.
In this case the drug prevents the production of a mutated version of the protein called transthyretin (TTR), which is responsible for the overproduction of amyloids. As a result of their buildup, people can suffer peripheral nerve damage or polyneuropathy.
"This approval is key for the RNAi field," James Cardia from RXi Pharmaceuticals in Massachusetts, which develops RNAi treatments, told Nature. "This is transformational."
The story of RNAi goes back 20 years to when the method was first discovered. Since then, RNAi has seen both highs (including a Nobel prize) and lows (including investment cutbacks).
Part of the problem in getting the technique working has been delivering RNA molecules into target organs without the degradation that normally happens in the bloodstream. One way around that, scientists discovered, is to pack RNA molecules in fatty nanoparticles that act as a shield.
This lets the adapted messengers collect in the liver, which is where the majority of transthyretin is produced.
In a clinical trial involving 225 people with hereditary transthyretin amyloidosis, average walking speed – usually impaired by nerve damage – was significantly improved for those patients receiving RNAi treatment to target transthyretin production.
The treated patients also showed higher muscle strength, faster reflexes, and better nutritional status than patients on placebos, even despite side-effects noted in the study.
With the approval of this drug, there is suddenly renewed hope for the roughly 50,000 people living with hATTR, and the loss of mobility, numbness, and pain that goes along with it.
"I've never been more optimistic about the future of RNAi," Douglas Fambrough, chief executive of RNAi company Dicerna in Massachusetts, told Nature. "All of those tear-your-hair-out days were worth it to get to today."
Now that the first RNAi treatment has been approved by the US Food and Drug Administration (FDA), scientists can turn their attention to getting the method working in other parts of the body, including the kidneys, brain, and spinal cord.
And unlike the genetic editing tool CRISPR, RNAi requires no permanent changes to a person's DNA, which has made it suitable for making subtle changes to crops as well as showing huge potential for treating human disease.
"This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms," says FDA Commissioner Scott Gottlieb.
"New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses."
The results of the patisiran clinical trial were published in the New England Journal of Medicine in July.