Sergio Crespo-Garcia, Maisonneuve-Rosemont Hospital Research Center
Winner of the Marlene Reimer Brain Star of the Year Award, as the number one ranked winner of 2024
Scientific publication
Crespo-Garcia S, Fournier F, Diaz-Marin R, Klier S, Ragusa D, Masaki L, Cagnone G, Blot G, Hafiane I, Dejda A, Rizk R, Juneau R, Buscarlet M, Chorfi S, Patel P, Beltran PJ, Joyal JS, Rezende FA, Hata M, Nguyen A, Sullivan L, Damiano J, Wilson AM, Mallette FA, David NE, Ghosh A, Tsuruda PR, Dananberg J, Sapieha P. Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. Nature Medicine 2024 Feb;30(2):443-454. doi: 10.1038/s41591-024-02802-4. Epub 2024 Feb 6. PMID: 38321220.
Links
Discovery of a new therapeutic avenue to protect vision in diabetic patients.
Diabetes is a silent epidemic with profound complications in the retina, including a profound visual impairment that robs individuals of their ability to connect with the world around them. Dr. Sergio Crespo-Garcia, working as a post-doctoral fellow in the laboratory of Dr. Przemyslaw (Mike) Sapieha at the Maisonneuve-Rosemont Hospital Research Center, has identified a novel therapeutic strategy aimed at reversing diabetic macular edema (DME), a pervasive blinding condition in diabetic patients. This new therapeutic approach has the potential to be applied to other neurodegenerative diseases.
Specifically, Dr. Crespo-Garcia and his colleagues investigated the role of cell aging (senescence) in the development of diabetic macular edema (DME). They showed that senescent cells play a critical role in driving leakage from blood vessels and neuroinflammation of the retina leading to retinal damage in diabetes. Further, they identified a protein, called B-cell lymphoma extra-large (BCL-xL), as a potential target to selectively eliminate senescent cells. By employing foselutoclax (UBX1325), a small molecule drug, they demonstrated reduction in retinal neuroinflammation and improvement in vascular and neuronal function. Importantly, these preclinical data translated to human trials where patients enrolled in the Phase 1 trial showed a gain in visual acuity – these were patients for whom other treatments were no longer beneficial. Most excitingly, Phase 2 trials are currently underway, and could transform the way we protect vision in diabetic patients.
The therapeutic approach identified by Dr. Crespo-Garcia can lead to disease modification itself which is very impactful given that at least 40% of patients do not respond to currently available DME treatments. The significance of this work lies in its impact on a highly prevalent cause of blindness associated with diabetes, but it also sets the stage for future research into the broader implications of cellular senescence in other brain diseases.
About Sergio Crespo-Garcia
Dr. Sergion Crespo-Garcia performed this research as a post-doctoral fellow in the laboratory of Przemyslaw (Mike) Sapieha at the Maisonneuve-Rosemont Hospital Research Center, affiliated to the Université de Montréal. He performed most of the research and lead the team of researchers performing the preclinical studies. He is now an Assistant Professor at the School of Optometry, Université de Montréal, and his laboratory studies faulty interactions between vascular and perivascular cells in the retina that can lead to neurodegeneration.
Before joining Dr. Sapieha’s team, Dr. Crespo-Garcia received international training in Spain, United Kingdom and Germany. He participated in the European Commission Marie Curie ITN project REVAMMAD to improve the diagnosis, modeling and understanding of retina vascular disease. During that time, he earned his PhD in Biomedicine from the Charité Universitätsmedizin Berlin, where he was awarded with the Dr. Margot Engelmann Stiftung prize for his doctoral work in experimental ophthalmology.
Overall, Dr. Crespo-Garcia’s work has contributed to characterizing neuroinflammation and cellular senescence in the retina in the context of retinopathies and paved the way to novel therapeutic approaches such as senolysis, presented in this paper. Outside the laboratory, Dr. Crespo-Garcia is a ceramist, and collects and catalogs insects.
Source of funding
P.S. holds the Wolfe Professorship in Translational Research, a Canada Research Chair in Retinal Cell Biology as well as the Fonds de Recherche en Ophtalmologie de l’Université de Montréal Endowed Chair. S.C.-G. holds a fellowship from the Fonds de Recherche du Québec – Santé (FRQ-S) and the Montreal Diabetes Research Center. This work was supported by UNITY Biotechnology. Other funding was provided from operating grants to P.S. from Diabetes Canada (DI-3-18-5444-PS), the Canadian Institutes of Health Research (Foundation grant 353770), The Alcon Research Institute Senior Investigator Award and The Heart and Stroke Foundation of Canada (G-16-00014658) and BrightFocus Foundation (M2022015I). Additional support was provided by the Fonds de Recherche en Ophtalmologie de l’Université de Montréal (FROUM), the Réseau en Recherche en Santé de la Vision (RRSV) and the FRQ-S/RRSV-funded Single-Cell Academy.
