A needle-free way of treating retinal diseases
Diabetic retinopathy and age-related macular degeneration (AMD) are two major eye diseases that can lead to severe vision loss. They are also two conditions that are impacting more and more people. It is estimated that 420 million people already live with some type of retinal disease. However, this number is expected to grow significantly in the coming decades due to both a globally ageing population and the increasing prevalence of diabetes. The gold standard for treating diabetic retinopathy and AMD is repeated intravitreal injections directly into the eye. Although effective, these injections are invasive and expensive, and place a significant burden on patients, healthcare systems and clinicians. “Orally administered drugs could offer an easy-to-administer, less invasive and more acceptable alternative to the injections currently used to treat these diseases,” says Krisztián Kovács, principal investigator from the Translational Retina Research Group(opens in new window) at Semmelweis University(opens in new window). The EU-funded NeoVasculoStop(opens in new window) project is leading an effort to develop such an alternative.
A promising new class of active pharmaceutical ingredients
The project, supported by the European Innovation Council(opens in new window) (EIC), designed, synthesised and tested a new class of active pharmaceutical ingredients that could be used in an orally administered drug. Amongst these ingredients are 25 molecules capable of binding to their receptor in a light-dependent manner. “Our newly developed active pharmaceutical ingredient class was found to have a strong chemical structure-bioactivity relationship, and the molecules showed efficacy in both biochemical assays and cellular systems,” notes Kovács, who served as the project coordinator. One lead molecule was tested in rodents and rabbits, while a follow-up molecule was tested in rodents. According to Kovács, particularly encouraging results were achieved in in vivo experiments using very low doses of both molecules. “One of the project’s most notable achievements is that these in vivo results were obtained at such low doses, providing a strong foundation for further development,” he explains. The project also confirmed the photoinduced enhancement of inhibitor potency, as well as the ideal structural properties for the visible-light photoactivation of oxindole derivatives. The project’s innovations were evaluated by the European Commission’s Innovation Radar(opens in new window), which identified project partners Semmelweis University and Vichem(opens in new window) as being ‘key innovators’.
A patient-friendly treatment for serious retinal diseases
By developing a new class of photoactivatable molecules, the NeoVasculoStop project has laid the groundwork for creating an injection-free and thus patient-friendly way of treating diabetic retinopathy and AMD. “Not only did we create a promising new molecular platform for treating serious retinal diseases, we also generated a pipeline of novel molecules, identified lead and follow-up compounds, and provided preclinical evidence to support further development,” concludes Kovács. With a focus on moving its lead compound towards clinical development, the project is now applying for an EIC Transition grant(opens in new window), organising Good Manufacturing Practice(opens in new window) based production, and conducting safety studies. They are also defining the structure and objectives of a planned first-in-human clinical trial. The new family of molecules has been patented.
