What if viper venom could fight diabetic retinopathy and AMD?

Snake venon: A complex and highly effective substance

Snake venoms consist of a complex mixture of proteins with diverse properties, evolved for specific functions such as defense and prey capture. They are a rich source of potent, targeted molecules that provide valuable tools for a deeper understanding of complex biological processes, including inflammation, angiogenesis, neurotransmission, and immune response. Due to their molecular diversity, snake venoms enable precise targeting of promising therapeutic pathways, offering potential for the development of novel, innovative treatments. This makes snake venoms an invaluable resource for medical research.

Lebecetin, a biomolecule of interest and promise

Lebecetin, a protein extracted from the venom, has anti-angiogenic properties, meaning it inhibits the formation of new blood vessels. This mechanism is crucial not only in tumor development but also in retinal pathologies like wet AMD and diabetic retinopathy, where abnormal blood vessel growth can cause retinal damage and vision loss.

Research conducted at the Institut de la Vision has shown that Lebecetin binds to and blocks integrins—proteins involved in blood vessel formation and stabilization. The results demonstrated that Lebecetin effectively reduced choroidal and retinal neovascularization in preclinical models of AMD and diabetic retinopathy. Currently, treatments targeting VEGF (vascular endothelial growth factor), a protein that triggers the formation of new blood vessels, do not work for all patients. In fact, around 10% of AMD patients and 30% of diabetic retinopathy patients develop resistance to these treatments. Lebecetin could therefore offer a therapeutic alternative by targeting other mechanisms of angiogenesis.

With no significant impact on mature blood vessels, lebecetin presents a strong safety profile, making it a promising candidate for treating the proliferative forms of AMD and diabetic retinopathy.

Indo-French cooperation to speed up transfer to patients

With the support and funding of SATT* (Technology Transfer Acceleration Companies), Dr. Xavier Guillonneau's team has tackled a number of challenges.
The first challenge was to synthesize and produce the research-grade protein on a large scale, with the same efficiency as that found in natural venom. This is crucial, as the molecule occurs in too small quantities in the venom to be used on a human scale.
The second challenge was optimizing the formulation to develop the most suitable drug delivery system: a slow-release injectable form. SATT found the ideal partner for this phase: the Indian company Lamark Biotech, which offers a patented technology that creates a gel containing the drug. This gel is then transformed into small crystals that trap the active molecules, preventing their degradation and allowing for slow, prolonged release.

The development phase is ongoing and is funded by several sources, including the European Union through the "Marie Curie" program, with support from Genethon, as well as by CEFIPRA**, a scientific cooperation program between France and India. This funding has allowed the continuation of research, particularly with the addition of  Dr Avtar SAIN, an Indian postdoctoral researcher, to the team. Avtar's work focuses on optimizing key stages of production to ensure a protein that meets medical-grade standards. For clinical trials in humans, it is essential to eliminate any modifications introduced during the research phase in order to purify the protein and ensure its study under optimal conditions (such as recognizing it once injected, monitoring it, and analyzing the results).

“The development of Lebecetin as drug molecule requires the critical parameters such as characterization of the molecule for its biophysical and functional properties. Hence, we are focusing on the method development for the in-house production and purification of lebecetin under GLP like conditions (Good Laboratory Practice) and characterization in compliance with regulatory authorities. The method development for characterization will provide a base for quality control of the lebecetin for batch to batch quality assessment. Further, the Lebecetin will be studied for its binding affinity and pharmacokinetics. Moreover, the well characterized Lebecetin will be formulated using the Lamark’s unique formulation technology. The formulated drug product “Lebecetin” will be evaluated for its quality, stability and functionality by In-vitro and ex-vivo assays developed during this period, prior to preclinical studies AMD model.” Avtar SAIN

The progress made so far, coupled with the commitment of all involved partners, offers promising prospects. If all goes as planned, this molecule could play a pivotal role in treating retinal diseases and other conditions that require innovative solutions. The clinical future of this research holds great promise for patients. The new formulation of lebecetin may also allow for longer intervals between eye injections.

*SATTs: Technology Transfer Acceleration Companies, created as part of the Investments for the Future Program. They finance the technological development of innovations resulting from French public research through an exclusive investment fund. As local and trusted entities, they detect, evaluate, protect, and bring these inventions to market, either by licensing them to existing companies or founding new startups.
**CEFIPRA: Franco-Indian Centre for the Promotion of Advanced Research is a bilateral scientific cooperation program between France and India, supported by the Ministry of Foreign Affairs of the French government and the Department of Science and Technology of the Indian government.