Approximately 40 % of perinatal blindness can be attributed to ROP, a potentially blinding eye disease that primarily affects premature infants weighing around 1 250 grams or less that are born before 31 weeks of gestation. In effect, the smaller the baby at birth, the more likely it is to develop ROP. The disorder usually affects both eyes and is one of the most common causes of visual loss in childhood, leading to lifelong vision impairment and blindness. The treatment of ROP, specifically ablation of the avascular retina with laser photocoagulation, has remained fundamentally the same for almost 50 years. In addition, these treatments are also damaging – they destroy the peripheral (non-vascularised) parts of the retina and can lead to a partial loss of peripheral or side vision. Developing the drug This is where the EU-funded PREVENT-ROP (New approach to treatment of the blinding disease Retinopathy of Prematurity (ROP)) project comes in. The overall aim of this project, consisting of 10 partners from five EU Member States, was to develop a novel preventative pharmaceutical intervention for ROP and other complications of prematurity, thus relegating the standard but destructive treatment of laser photocoagulation unnecessary. “When preterm children are deprived of their natural intrauterine environment they lose important factors, normally found in utero, such as proteins, growth factors and cytokines. It has been demonstrated that insulin-like growth factor I (IGF-I) is one such factor, but it is likely there are others,” explains project coordinator Prof Ann Hellstrom. “During foetal life these elements are introduced through placental absorption or ingestion from amniotic fluid (AF). The deprivation of such factors is likely to cause inhibition or improper stimulation of important pathways, which may cause abnormal vascular growth in several organs, such as the lungs and brain - the hallmark of retinopathy of prematurity (ROP).” For the PREVENT-ROP team, it was vital to understand which factors are lost with preterm birth and then to evaluate their impact on the development of ROP. This would have much greater implications for the growth and development of other organ systems, such as the brain, lungs and gut. The team believed that replacing lost factors would likely improve the overall development in these organs, and this was what their proposed treatment was designed to do. Caution required However, it wasn’t easy going for the team, since they were working with an extremely vulnerable patient group. “This project definitely required extreme caution,” says Prof Hellstrom. “A large multicentre trial in a very delicate intensive setting, like neonatal care, is a difficult clinical path to travel and required participants from academia and industry that are generous and understand each other’s driving force and aims in participating in such a project. In this project, we have been very lucky to have worked with highly scientific industry partners that has enabled us to develop a drug that can possibly improve the outcome for this vulnerable group of preterm infants.” Moving forward, a Phase II trial is due to begin in Q1 2019 and the project’s academic partners are planning a new neonatal trial aiming to improve outcome for preterm infants. “Overall, I’m extremely proud to have been the coordinator of a project that has seen high-quality collaboration between academia, SMEs and ‘Big Pharma’ in both Europe and the United States, and now where we are ready and able to conduct high-quality neonatal trials,” Prof Hellstrom concludes.
PREVENT-ROP, Retinopathy of prematurity, ROP, clinical trial, neonatal care