How ticks are helping to cure heart disease
BHF researchers are investigating how ticks - tiny blood-sucking parasites, could help us cure heart disease. Professor Shoumo Bhattacharya tells Sarah Brealey about his work.
Great ideas can come from unlikely places. For Professor Shoumo Bhattacharya, inspiration takes the form of a tiny animal that has been around for millions of years, but could soon help people with serious heart problems.
You’d probably rather not think about ticks – unless a pet dog or cat has forced you to confront them. There are more than 900 varieties, only some of which feed on humans, but they all live by sucking blood. You might have heard of them as carriers of Lyme Disease. But it seems that there could be a positive side to the tick.
These are remarkable creatures, explains Professor Bhattacharya. “Ticks have been around since before the time of the dinosaurs. They have been evolving for a long time to suck blood from many different animals.”
How ticks get around the immune system
If your dog gets a tick (or if you do after walking in the countryside), it probably doesn’t notice. For the professor, that’s a crucial detail. “If you have been bitten by a mosquito, you know quickly that you’ve been stung,” he says. “But a tick is different. They need to feed off you for a long period of time, usually eight to 10 days, during which they grow from a tiny tick to a big fat tick, and then they drop off and prepare for the next stage of their life cycle. So they have ways to make sure you don’t notice.”
The secret of this lies in the saliva the tick injects when it bites. Professor Bhattacharya says: “They inject more than 3,000 different small proteins, which block pain and inflammation.” Inflammation is an important part of the processes involved in many types of heart disease, as your immune system responds to the heart condition. It also causes the red, itchy bump you get after a mosquito bite. But you won’t get this after a tick bite – ticks have found a way to get around the immune system.
Using tick saliva to prevent inflammation
One aspect of the immune system involves chemokines, which act like signals in the body to bring cells to the right place.
When there is an infection or injury in the heart, such as a heart attack, chemokines are produced. They act as a signal to white blood cells, which travel to the area of the body where they are needed. But they can overreact and cause inflammation in the heart – this can affect how well the heart pumps and can even be fatal. Inflammation in the heart may then cause more chemokines to be produced. So it’s a vicious circle.
Tick saliva contains substances called evasins, and these block the action of chemokines. “The way evasins work is very clever,” says Professor Bhattacharya. “What they do is to take down many different chemokines. The chemokines network is a bit like the internet. If you take out one server not much will happen, you will still get emails. You have to take out lots of servers, or many chemokines. And tick evasins can do that.”
The chemokines network is a bit like the internet. If you take out one server not much will happen... You have to take out lots of servers, or many chemokines.
Perhaps fortunately, Professor Bhattacharya’s lab isn’t full of ticks, and no ticks are harmed in this research. Originally, tick saliva could only be extracted in tiny quantities using a miniature tube. But his team have worked out a way of inserting the genetic information from tick salivary glands into yeast (the same kind of yeast used for brewing), so that the yeast produces the evasins on its surface. Professor Bhattacharya has a picture of Charles Darwin hanging in his office, and says he is fascinated by evolution.
“The evolutionary aims of every organism are the same,” he says. “They develop mechanisms either to defend themselves or to prey more effectively on something else.
“With ticks, you can see interaction between species. Humans develop chemokines and complex networks to stop parasites and infections. The parasites respond by evolving so they don’t trigger an immune response. They start producing very complex proteins which act in really interesting ways to neutralise chemokines.
“What is really amazing is that these proteins don’t just work on humans, but also the other animals that the tick feeds on.”
Yara Alenazi, a doctoral student in Dr Bhattacharya’s lab, is working to identify new evasins
Ticks and myocarditis
The immune system plays a crucial role in myocarditis, a rare heart condition that can be fatal. The initial trigger can be one of several things, such as a viral infection that appears to be mild. But it’s the immune system response that causes the real problem. The heart muscle can become severely inflamed, and in some cases an apparently fit and healthy person can drop dead without warning.
It took me a long time to even convince my colleagues here in Oxford it was going to work. Now everyone is convinced
Although rare, myocarditis is one of the leading causes of sudden death in young adults. Currently, there is no treatment. But Professor Bhattacharya thinks tick saliva might hold the secret.
He is now working with a drug company to develop a new treatment. New drugs must go through development and testing, so it will be several years before it could be available for patients.
This research could have uses beyond myocarditis, including helping to reduce the damage caused after a heart attack. Professor Bhattacharya is planning to study how it could help vasculitis, a disease in which the immune system attacks healthy blood vessels sometimes causing serious illness. But his work could help with many other conditions, too. “Any condition which ends in ‘-itis’ is caused by chemokines, including arthritis and pancreatitis,” he says.
The importance of flexible funding
Professor Bhattacharya has been funded by the BHF for most of his career. Since 2009, he has been BHF Chair in Cardiovascular Medicine at the University of Oxford. He explains how the unique nature of BHF funding has allowed this research to happen.
“All this work is BHF-funded. Being awarded a BHF Chair was excellent because it gave me discretionary money, which I was able to spend on whatever interested me,” he says. “With most research grants, you have to write an application for that specific project, which a peer review committee is going to accept. That can be difficult to do: they may say ‘this is not going to work’. This work would have been turned down for a project grant, because to be honest it is slightly off the wall!
“Getting flexible funding that encourages innovation is hugely important. It took me a long time to even convince my colleagues here in Oxford it was going to work. Now everyone is convinced.”
Other ways nature is helping tackle heart disease
The first ACE inhibitor, captopril, was based on an ingredient found in the venom of the poisonous Brazilian viper.
Warfarin is used as an anticoagulant to reduce the risk of blood clots, but originally came from sweet clover plants. It was discovered after healthy cattle started dying from internal bleeding. Research revealed they’d been eating too much hay made from sweet clover.
These common flowers produce digoxin, which is toxic to potential predators, but can also be used as a treatment for people with atrial fibrillation.
The original source of many drugs, including ciclosporin, which is given to heart transplant patients to stop their immune system rejecting the new heart.