Gene Silencing: A New Frontier In Medicine?

Could inherited diseases now be treated by a newly-developed treatment called “gene silencing"?

By: Ringo Bones

Gene silencing had shown really promising results after a recent trial treatment to treat an inherited disease called porphyria – a crippling illness often linked to the madness of King George III. Patients with prophyria participating in the trial treatment of a new drug saw attacks of crippling pain reduced by 90-percent on average with half of them had resulted in the elimination of chronic pain. Porphyria is an inherited disorder which means people with the disorder cannot produce haem – a vital component of hemoglobin in red blood cells that transport oxygen around the body – and therefore suffer a painful buildup of chemicals called porphyrins. In the 1960s, psychiatrists suggested that the inherited illness might explain the mania suffered by King George III, based on evidence that he had purple urine which is a main symptom of the disorder.

The newfangled treatment uses an approach called gene silencing. A gene is part of our DNA that contains the blueprint for making proteins, such as hormones, enzymes or raw cellular building materials. But our DNA is locked away inside a cell’s nucleus and kept apart from a cell’s protein-making factories. So our bodies use a short strand of genetic code, called messenger RNA, to bridge the gap and carry the instructions. This drug, called givosiran, kills the messenger in the process known as RNA interference. In acute intermittent porphyria, the drug lowers the levels of an enzyme involved in haem production and prevents the buildup of toxic proteins.

Prof. David Rees from King’s College London treated patients taking part in the trial in the UK. He told the BBC that “this is a really important treatment   - it’s innovative. Porphyria is one of the first conditions it has been used successfully. I’m genuinely surprised how well it works in this condition and I think it offers a lot of hope in 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”. Other ongoing trials have shown that the gene silencing drug givosiran has the potential to treat other inherited diseases but it is still in its very early days. A similar approach is also being investigated in Huntington’s disease, which is caused by a buildup of a toxic protein that kills brain cells. Researchers are also looking into it as an alternative to statins for lowering cholesterol.