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New class of medicines shows promise

'Gene silencing' spares patients the crippling pain of intermittent porphyria

Mark Gould

Monday, 15 April 2019

A new type of medicine called "gene silencing" is being used to reverse intermittent porphyria - a disease that leaves people in crippling pain and is sometimes fatal.

The novel approach fine-tunes the genetic instructions locked in our DNA.


Doctors told the BBC that they are "genuinely surprised" how successful it is and that the same approach could be used in previously untreatable diseases.

There are several types of porphyria, but each is caused by the body being unable to produce enough haem which can lead to a build-up of toxic proteins. These cause the attacks of physical pain in some forms of the disease while in others the proteins can cause skin problems. There is some speculation King George III had porphyria.

“Gene silencing” leaves the original DNA alone but targets the instructions that are sent out into the cell in the messenger RNA. However, treatment is not a one-off and a drug called givosiran must be taken to keep the therapy working.

A clinical trial* on 94 people across 18 countries was presented at the International Liver Congress in Vienna on Friday which demonstrated that the therapy cut the number of severe attacks by 74%. And 50% of patients were completely clear of attacks that needed hospital treatment, compared to 16% given a dummy treatment. One person dropped out of the study due to side effects.

Professor David Rees, from King's College London, treated patients taking part in the trial in the UK. He told the BBC: "This is a really important treatment - it's innovave. Porphyria is one of the first conditions it has been used in successfully.

"I'm genuinely surprised how well it works in this condition and I think it offers a lot of hope for the future."

"Gene silencing" has been used to treat a genetic disease that causes nerve damage and the US Food and Drug Administration said such medicines "have the potential to transform medicine". A similar approach is also being investigated in Huntington's disease, which is caused by a toxic protein that kills brain cells. Researchers are also looking into it as an alternative to statins for lowering cholesterol.

Barry Greene, the president of Alnylam, which developed the porphyria drug, told the BBC the latest findings were "heralding a brand new class of medicine".

Dr Alena Pance, from the Wellcome Sanger Institute, told the BBC News website: "I get excited about this, because targeting the messenger RNA allows the fine-tuning of the proteins that are involved in certain diseases.

"And therefore, perhaps for the first time, [it can] offer a tool to be able to control those diseases to very accurate levels.

"There are diseases that are very difficult to find treatment for, that with this technology might be possible to tackle."


*ILC 2019: Promising results reported with givosiran in acute hepatic porphyria (AHP) and lanreotide in polycystic liver disease (PLD) associated with autosomal dominant polycystic kidney disease (ADPKD). Presented at the EASL confernece, 13 April 2019, Vienna, Austria.

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