A perfect case study of CRO – Pharma successful alliance

ZeClinics and Dompé Farmaceutici started this collaboration a few years ago, in an effort to validate the use of zebrafish to reliably model human retinopathies and, most importantly, to test potential therapeutic approaches. As a result, the partners have recently co-published an article demonstrating the retinal regenerative role of recombinant human nerve growth factor (rhNGF) in the zebrafish model of retinal degeneration. This initial successful collaboration has led to multiple unrelated projects between both partners.

 

NGF is an FDA and EMA-approved drug for neurotrophic keratitis, a rare eye disease that can lead to loss of sight. Increasing lines of evidence have shown that NGF can be crucial for the treatment of blinding diseases, such as retinal degenerations, and several studies have already described the protective effect of NGF administration. Thus, this is a perfect case study of ZeClinics involvement in repurposing projects, discovering new indications for clinical or marketed drugs.

 

So far, the use of zebrafish to test drug delivery for retinopathy treatments is scarce. However, unlike mammals, which cannot regenerate their retina after damage or degeneration, the zebrafish retina displays a robust regenerative response upon injury, and this feature can be exploited to gain insights into molecular mechanisms underlying healing of damaged tissues in eye human pathology.

 

Dompé Farmaceutici is an excellent example of a pharmaceutical company who decided to bet on the advantages of this alternative model to gain more insights on the mechanism of action of FDA-approved rhNGF. Specifically, the aim of the project was to assess the potential regenerative effect of intravitreal (IV) administration of rhNGF using a retinal degeneration paradigm in adult zebrafish based on constant light irradiation. The results demonstrate the highly conserved nature of NGF canonical pathway in adult zebrafish retina and that administration of rhNGF can boost zebrafish retinal regeneration upon injury.

 

To date, vascular endothelial growth factor (VEGF) inhibitors are the most widely used compounds for the treatment of intraocular disorders. Nonetheless, amelioration of patients’ condition is subject to frequent injections throughout several years, representing a heavy burden on health systems. For this reason, there is a need for more effective and long-lasting treatments that can be implemented in clinical settings. Importantly, this study has shown that a single intravitreal injection of rhNGF is able to lead to a mild amelioration of damaged zebrafish retinal tissue in a short time window, likely due to enhanced cell proliferation.

In light of these data, ZeClinics and Dompé Farmaceutici propose the zebrafish as a powerful alternative model for testing the efficacy of novel potential IV-injection based treatment of retinal diseases, with the possibility of medium-throughput assessment of toxicity and pharmacokinetics.