Dr Rebecca Burton, who led the research and is funded by us, said: “The starting point was a chance observation. A patient being treated for Lupus also had a high heart rate. When the patient started Hydroxychloroquine for the Lupus, their heart rate reduced. We started to think about how the drug might be acting in the heart and began extensive pre-clinical studies."
The researchers found that the drug acts on an area of the heart called the sino-atrial node. This group of cells keeps the heart beating by producing a rhythmic electrical signal that is transmitted to the rest of the heart muscle. The drug targets a particular protein in this region of the heart to restrict an electrical signal known as the ‘funny current’ that is especially important in setting the heart rate.
The effects of HCQ on the heart were studied in the late 1950s but initial findings were not followed up. There were also reports of lowered heart rate as a side-effect in patients treated for other conditions, but the potential of this drug as a heart treatment had not been pursued fully until the Oxford team began their research.
Dr Burton said: "The number of drugs on the market and the number of possible conditions are so huge that it takes a lucky observation to connect something which might be viewed as an annoying side-effect to something which could have a clinical benefit.”
HCQ has a well-established safety profile. Side-effects are limited and well understood, and it is possible to use it for children and pregnant women under specialist care.
Professor Jeremy Pearson, our Associate Medical Director, said: “This study is an elegant example of how a chance clinical observation, carefully followed up, can provide evidence in favour of an unexpected new use for an old drug. However, a clinical trial is needed to establish whether HCQ is as safe and effective as existing medicines used to reduce heart rate.”