27th January 2017
Dr Roberto Solari has over 29 years of research and drug discovery experience. He was involved in forming two of the UK’s most successful biotech start-up companies and was Vice President of Biology in the Respiratory Therapy Area at GSK (GlaxoSmithKline). He left GSK in 2015 to join us full time at the MRC-Asthma UK Centre and he is based at Imperial College.
Roberto kindly provided us some insight into his latest research, which is trying to stop colds and other viruses from causing asthma attacks.
“Asthma attacks are often caused by viral infections of the upper respiratory tract. There are a number of common viruses that are responsible including influenza (flu), respiratory syncytial virus (RSV) and the common cold virus (rhinovirus). Viruses do not respond to antibiotics and it has been very difficult to discover effective anti-viral drugs, as these viruses are very good at mutating to avoid the treatment of drugs.
In order to survive and spread, viruses reproduce by invading and taking over our cells. When they enter our body via the airways, they attach themselves to the cells that line the surface of our airways where they inject their “gene”. The virus’ gene then hijacks the area of the cell used to keep it working properly and re-programmes this area to make more copies of the virus. The newly formed viruses then go on to invade neighbouring cells and that’s how the infection spreads.
Viruses and humans have co-evolved over many millions of years and our cells have developed clever defence mechanisms. Our cells have sensors that detect when they have been invaded by a virus and they produce defence proteins that block the virus and recruit white blood cells to the site of infection. This is our body’s immune response to fighting the virus and protects us from future infections, but unfortunately this response also causes inflammation, which will cause many of the symptoms people experience when they have a respiratory infection. In most people these symptoms only last for a few days and eventually our immune system wins, and the infection is resolved and we feel better. However, people with asthma don’t cope so well.
For people with asthma, symptoms of infection with the cold virus are worse and last for much longer and can lead to an asthma attack. This battle between the virus trying to take over our cells and the cells trying to fight back is complex, and viruses have in turn evolved ways to block the cell’s defence mechanisms.
The research in our lab is aimed at understanding why people with asthma are not as good at fighting these viral infections. We now understand some of this complex tug-of-war and how this may be different between people with and without asthma. My team at the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma are studying this ‘people versus virus’ battle in several ways. At the patient level, we are infecting volunteers with and without asthma with the common cold virus and measuring how their lung function and symptoms differ over the course of the infection. We are also taking cells from their blood and lungs to perform biochemical and genetic tests to try and discover the cause of the different responses between people with and without asthma. Armed with this knowledge, we believe we will be able to develop better therapies for people with asthma suffering from a viral infection.
My team also working inside the cell trying to understand at a molecular level how the virus hijacks the cell. We are also studying what components inside the cell the virus needs to take over in order to make more copies of it.
My aim is to make drugs that block this hijack and so stop the virus from taking control of the cell and reproducing. We have some promising early results and hope that one day these will translate into anti-viral medicines.
There are many challenges to overcome before we find a safe and effective anti-viral medicine to prevent asthma attacks. Once you have found a good target, making a drug that hits that target and is safe to give to people is a difficult and expensive process that takes many years. So far, we have found a target that when blocked with a chemical, can stop viruses from replicating in cells. This gives us hope that a drug discovery is possible. If we can make a safe and effective drug, it will be crucial that people with asthma take the drug early enough in their infection if it is going to have an impact on preventing asthma attacks. But even when you have developed a drug, viruses can mutate to bypass the action of the drug.
Despite all these challenges, we believe there is a real patient need and the opportunity to make a difference. With the support of Asthma UK we will continue with this promising research.”