Creating a wet AMD drug using flower compounds

Prof Dulcie Mulholland, University of Surrey and Prof Tim Corson, Indiana University - £196,339

Current drugs available for wet AMD are extremely valuable and have helped maintain vision in many people. However, not all patients treated with these anti-VEGF injections respond well to them. Different types of drugs need to be available for these people. This research aimed to test whether a group of compounds called 'homoisoflavanoids', found in rare hyacinth plants, may be able to stop blood vessel growth in the macula.

What did the researchers do?

The team improved upon previous methods to better synthesise a number of homoisoflavonoids. They were able to produce these compounds on a greater scale and at a lower cost. Having developed this improved protocol, they went on to screen 63 homoisoflavonoids for their ability to stop the growth of blood vessels and also for toxic effects on healthy eye tissue.

What did the researchers find?

The researchers found 26 compounds that blocked the growth of blood vessel cells. Six of the more promising compounds were then tested in follow up screens of blood vessel growth activity and showed dose-dependent inhibition, meaning a higher dose led to greater inhibition. Using computer programmes, the researchers were able to predict and model the important parts of the molecules and investigate how they work.

They found some of the more promising homoisoflavonoids might act by binding to an enzyme in the cell that is important for blood vessel growth. By binding to and blocking this enzyme, the homoisoflavonoid acts to inhibit its function and thus prevent blood vessel growth. However further work is still needed to assess this.

How can this help and what’s next?

The team generated extensive data to help select molecules for studies using animal models of abnormal blood vessel growth in the eye. Their goal is to take promising compounds which could potentially be used to treat wet AMD into clinical trials.