Brain injury occurs in 30% of infants born preterm birth, with children having increased risk of developing cerebral palsy, autism spectrum disorder, attention-deficit hyperactivity disorder or other general disorders of thought or behaviour. This affects both the individual and their family throughout life. The injury in these patients has been shown to be highly correlated with an increased inflammatory response at, and following, birth. Currently there are very few therapies that limit injury in the at-risk patients; we have identified Montelukast as a potential protective therapy for these children. Montelukast has anti-inflammatory properties; our preliminary work in a mouse model of preterm brain injury shows that Montelukast treatment reduces inflammation in the body and the brain. It also reduces behavioural abnormalities in later life, and the injury observed in number of specialised cell populations in the brain.
Montelukast is already used in paediatric patients with asthma, and has been shown to be safe with few side effects, making it an attractive option for use in preterm babies to reduce brain injury. Before we can conduct a clinical trial testing this drugs in humans we need to know how much of the administered drug reaches the brain, and what effect it has on the normal and abnormal development of each brain cell population. To do this we will administer an effective dose of Montelukast to mouse pups and measure how much drug gets to the blood and the brain. We will then test these concentrations of Montelukast in cultures of cells taken from the brain, to confirm that Montelukast helps cells survive and grow in the presence of an inflammatory response similar to that seen in the preterm brain. We can use this information to ensure that we administer the right dose to patients in a clinical trial, a dose that has maximum possible positive effects and minimum possible side effects.