New treatment option for wet AMD

Dr James Whiteford, Queen Mary University of London - £148,991

May 2019 - April 2022

Research summary

Wet age-related macular degeneration (AMD) can lead to rapid sight loss. We currently have treatments which work well for most. However, for some people, the drugs don’t work. This project looks at a different way to treat wet AMD, which could help them.

What’s the problem?

While treatment with anti-VEGF drugs is current practice for patients with wet AMD, they don’t work well for everyone. Some patients don’t respond well, so more options need to be available. 

What did this project achieve?

The project was able to show that the protein they were testing, called syndecan-3, is able to inhibit blood vessel formation. The researchers were able to find the specific part of the protein that causes the effect and create a miniature version of the protein, which they named QM111. QM111 was then tested in models of wet AMD and was found to be able to stop the wet AMD model progressing and not have any toxic effects or inflammation. 

What’s next?

The researchers filed a patent for QM111 and plan to move forward to continue to research this as a new treatment for wet AMD. They are looking to conduct necessary work in order to move towards clinical trials, and are working with a company to take this forward. Alongside this, the team will continue to investigate how other syndecans may be involved in macular disease. 

Publications

Pessolano, E., Belvedere, R., Novizio, N., Filippelli, A., Perretti, M., Whiteford, J. & Petrella A “Mesoglycan connects Syndecan-4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro.” FEBS J (2021) 288(22):6428-6446
De Rossi, G., Vähätupa, M., Cristante, E., Arokiasamy, S., Liyanage S.E., May, U., Pellinen, L., Uusitalo-Järvinen, H., Bainbridge, J.W., Järvinen T.A.H., & Whiteford, J.R. “Pathological angiogenesis requires Syndecan-4 for efficient VEGFA-induced VE-Cadherin internalization” Arterioscler. Thromb. Vasc. Biol (2021) 41(4):1374-1389
Tsoyi, K, Liang, X, De Rossi, G, Ryter, S.W., Xiong, K, Chu, S.G., Liu, X, Ith, B., Esposito, A.J, Poli,S., El-Chemaly, E, Perrella, M.A, Shi, Y., Whiteford, J.R. & Rosas, I.O., “CD148 deficiency in fibroblasts promotes the development of pulmonary fibrosis” Am. J. Respir. Crit. Care Med. (2021) 204(3):312-325
Belvedere, R., Morretta, E., Pessolano, E., Novizio, N., Tosco, A., Porta A., Whiteford, J., Perretti, M., Filippelli, A., Monti, M.C. & Petrella, A. “Mesoglycan exerts its fibrinolytic effect through the activation of annexin A2.” J Cell Physiol. (2020) 236(7):4926-4943
Shaik F, Balderstone MJM, Arokiasamy S, & Whiteford JR. (2022) ‘Roles of Syndecan-4 in cardiac injury and repair.’ Int J Biochem Cell Biol. 146:106196
Gopal, S., Arokiasamy, S., Pataki, C., Whiteford, J.R. & Couchman, J.R. "Syndecan Receptors: Pericellular Regulators in Development and Inflammatory Disease" Open Biology (2021) 11(2).
Arokiasamy S., Balderstone, M.J.M, De Rossi, G & Whiteford, J.R. (2019) “Syndecan-3 in Inflammation and Angiogenesis” Frontiers in Immunology 10 (2019):3031

Patents

‘Antiangiogenic peptides from Syndecan-3’ Filed 2021 S Arokiasamy, G De Rossi and JR Whiteford