CXC chemokines in neovascular eye disease – CHEMO-NED

Angiogenesis inhibition has led to impressive results in clinical trials in a variety of human cancers. Most anti-angiogenesis strategies are based on the inhibition of VEGF. Another field where anti-angiogenesis treatments are important is ocular diseases associated with neovasculrization. Current treatments, based on the inhibition of VEGF are expensive (cf Lucentis) and may be of limited efficacy in some patients or after prolonged use. Thus, there is a need of cheaper and more efficient treatments for these conditions.
We are proposing a project related to the use of mutant CXC chemokines or fragments for the treatment of ocular neovascularization and associated diseases.
Chemokines are broad-range regulators that play important roles in development, inflammation, HIV pathophysiology, and cancer. Angiostatic CXC chemokines have an important role against tumor development and diffusion. Indeed, overexpression of CXCL4 and IP-10 blocks tumor progression and can also induce regression of metastasis. Partner 1's laboratory have extensively contributed in the study of CXCL4 chemokines and demonstrated many unique features of these molecules.
We will evaluate these molecules in murin models of neovascular disease by acute administration or chronic delivery systems. We will further determine the expression of differents chemokines in pathology in murine models and in samples from human patients.

The project is devided in three main tasks :

Task 1 : To investigate the therapeutic efficacy of CXCL4-Ms or derivatives in models of ocular neovascular disease
Task 2 : To analyze the effects of mutant CXCL4’s on cell signalling
Task 3 : To further validate our specific monoclonal anti-CXCL4/CXCL4L1 antibodies in ocular neovascular pathology

The project associates two teams that have complementary expertises. Team 1(Bikfalvi) is in expert in the field of angiogenesis and has a long standing track record in the study of the effect of chemokines in angiogenesis. Team 2 (Behar-Cohen) is an expert in the field of ophtalmological research and has a long-standing track record in particular on retinal and choroidal neovascular disease and drug delivery in the eye and non-viral gene therapy.

The project has adequate intellectual property protection through a number of patents. In the course of the project, a start-up should be set–up for the valorisation of the data generated. If necessary, co-development with an existing company will be done for a part of the innovation generated by the project.