It’s a combination that clearly motivates him: “It can be distressing when things go wrong for your patients and this is a major driver to improve or discover new treatments.” Or as one of Storey’s clinical research fellows, Dr Wael Sumaya describes it, “When you’re a clinician and you’re seeing one patient, you’re only helping one patient. When you’re doing research you have the potential to help millions of patients. It also helps your teaching – when you’re teaching students about your research you understand it better, which means you teach it better. That’s the beauty of combining academic and clinical work.”
In the 1990s, when Rob was fresh out of medical school and training to become a cardiologist, death rates from heart attacks were still very high, despite the development of technologies such as stents and pacemakers. Blood clots had only recently been discovered as the cause and aspirin became the standard treatment for preventing further clots. However, the relatively weak effects of aspirin had prompted a flurry of research into new anti-clotting drugs. One of the drugs clopidogrel would soon become the main drug prescribed to patients following a heart attack. However, there were drawbacks with clopidogrel, whether or not it worked was a complete lottery, based on a patient’s genetics and body characteristics. Storey was keenly aware of the drug’s shortcomings and the need for something better.
Enter pharmaceutical company Astra (later AstraZeneca), who had been working on a new intravenous anti-clotting therapy known as cangrelor, it was the precursor for ticagrelor. Recognising the potential of these drugs, Storey approached Astra to carry out research on cangrelor, he explains: “It was very exciting because the processes I was researching hadn’t been well-documented… it was completely unexplored territory.”
Cangrelor and ticagrelor function as platelet aggregation inhibitors, targeting and inhibiting the activation of the P2Y12 receptor on the surface of platelet cells, reducing their ability to clot. The receptor plays a profound amplification role in platelet activity. Rob describes its effect as being like a volume control. Activate the receptor and you turn the volume up. Block it and you turn the volume down.
“The advantage is that with cangrelor and ticagrelor you don’t switch the sound off altogether.” Rob outlines. “The platelets still have some activity – to stop bleeding you still need platelet activity. So it’s a very neat way of preventing clots forming in the arteries.”
Storey was initially the only researcher outside of Astra with access to cangrelor. Proving its effectiveness in the lab and demonstrating this to doctors and scientists around the world was his responsibility. And it was already showing a more consistent and reliable response in different blood samples – potentially a major step forward from the current treatment.
He was also the first doctor to ever administer it to a patient in the late 90s. “Although it was 20 years ago, I remember this brave gentleman who volunteered to take part in the trial after being admitted to hospital with a heart attack the evening before.” says Storey. “Starting the drug was an exciting moment as I felt there was a strong chance it was going to benefit him. We also gained a huge amount of information through blood sampling and testing how long he bled for whilst we gave different doses of cangrelor. I think patients who signed up for these studies had a sense of this pioneering work that was potentially going to help them. It’s so important to remember the dedication and courage of any patient who volunteers for clinical research, it allow us to improve treatments that will in the end benefit all patients.”
Rob went on to advise Astra on the process of turning cangrelor, a treatment administered through an intravenous drip, into ticagrelor – an oral treatment that could be prescribed for 12 months or more. Then came the immense challenge of helping in the design of a clinical trial to prove to the medical world the drug’s effectiveness.