Proof of Concept Success for the Targeted Prodrugs

Professors Roz Anderson and Paul Groundwater, with Pratap Suryadevara and Stephanie Cannell, University of Sunderland, UK, in collaboration with Professor William van’t Hoff, Great Ormond Street Hospital, London, UK.

Summary By John Terry.

The prodrug research sponsored by the Foundation at Sunderland University passed a highly significant milestone recently.

To recap, these prodrugs are chemically modified cysteamine (the active ingredient in Cystagon) designed to be transported round the body and be smuggled into cells where they will release cysteamine on the spot where it is needed. If successful this approach would lead to many fewer side effects and much lower doses because little would be lost through excretion.

Having proved that they are transported into normal kidney cells and release cysteamine inside them, it has now been shown that this also occurs with cystinotic cells where their ability to remove cystine was shown to be at least as good as cysteamine. These results, combined with the very low cell toxicity that they showed, are extremely encouraging.

However, there is still more work to be done before we have a usable medicine. Sunderland have made nine variants of their ideas but so far only one has been tested and shown to work in cystinotic cells. All should be evaluated to identify the best candidate. Then there are a number of standard and detailed toxicity tests that will be required before the best candidate can go forward to clinical trials. To reach that position the Trustees have recently made an award of over £93,000 to fund the work for three more years.

Read Professor Roz Anderson and her research team’s report on their latest results for Cystinosis Research: Proof of Concept Success for the Targeted Prodrugs