CAAIF Research Fellowship in Type 2 Inflammation
supported by Sanofi Genzyme Canada
Dr. Partho Adhikary
Th2 inflammation-on-a-chip: Developing an ex vivo drug discovery platform for atopic diseases.
Atopic diseases are common allergic diseases such as eczema, asthma or hay fever. Skin and lung cells produce a factor, thymic stromal lymphopoietin (TSLP), which is known to be a main driver of such atopic diseases as it activates immune cells that further trigger inflammation. Hence, inhibiting this factor holds a great potential to treat atopic diseases. Currently, mostly large molecules, such as antibodies against TSLP are being developed, which however must be administered by injection and cannot be applied locally, for example as a cream. Drugs which can be applied locally offer several advantages such as less side effects, being more effective, and higher acceptance rates among patients. Hence, we are currently developing effective so called ‘small molecule TSLP blockers’ with the goal to be able to apply them locally onto the skin without needing any needles or injections. We already have identified a few very promising candidates, yet there is no model available to test its safety and efficacy. Hence, we will develop a ’human-on-a-chip’ setup which will allow us to test the promising compounds in complex and novel human-based setting without any animal models.
CAAIF Research Fellowship in Type 2 Inflammation supported by Sanofi Genzyme Canada
Dr. Nermin Diab
Point of care solutions to delayed Type 2-mediated drug
Chronic cough affects approximately 10% of the general population and is one of the commonest reasons for referral to secondary care. Unfortunately, there are no licensed treatments for this debilitating condition, which affects the social, physical and psychological well-being of patients. Asthma and Non-asthmatic Eosinophilic Bronchitis (NAEB) are known causes of chronic cough. An important feature of both these conditions is the presence of an inflammatory cell called the eosinophil which is found in the airways. The most common treatment for this is high doses of inhaled steroids, but when the cough becomes unbearable, repeated courses of oral steroids are administered. However, many patients have persistent cough despite this treatment and can develop significant steroid related side effects. Developing treatment for this condition is thus a major unmet clinical need.
Cough is a defensive reflex which is triggered by activation of nerves which are found in the airway lining. Recent evidence suggests there is a significant increase in eosinophils in the airways which sensitizes these nerves. This makes the nerves more easily activated leading to more coughing. If these eosinophils could be depleted and prevented to enter the airways then we predict that the nerves will be less sensitive and coughing will be reduced.
Mepolizumab is an injection medication, which blocks a key chemical that prevents the maturation and activation of eosinophils. It is a licensed medication which is currently used in patients with severe asthma to prevent severe asthma attacks. However, there has been no evidence to show whether this medication would improve coughing. The aim of this research project is to investigate whether mepolizumab reduces objective cough frequency in patients with eosinophilic airway diseases. The results of this study would result in a paradigm shift in the management of this challenging condition and provide patients hope of an improved quality of life.