Retinal Stem Cell Clinical Trails: Are We There Yet?

Retinal Stem Cell Clinical Trails: Are We There Yet?

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By: Tahani Baakdhah

Dr. Mary Sunderland is a distinguished Institute of Medical Science (IMS) alumnus who completed her Masters of Science (MSc) thesis under the supervision of Dr. Derek van der Kooy. Following her graduate studies, Dr. Sunderland pursued a post-doctoral fellowship where she gained the experience necessary for her current dynamic and multi-faceted position as the Director of Research and Education at the Foundation Fighting Blindness (FFB). I recently had the opportunity to travel back in time with her and re-live the major highlights of her research career. As Dr. Sunderland revisits her career trajectory, she also provides an outlook on the future of research for treating blindness.

During the last year of her undergraduate studies, Dr. Sunderland became fascinated and intrigued by developmental biology. She completed a double major in zoology and philosophy, and thought of developmental biology as the perfect intersection of these two disciplines of study. Following her undergraduate studies, Mary joined Dr. van der Kooy’s lab in the landmark year of 2001, in which he published his discovery of retinal stem cells. In the van der Kooy lab, Mary evaluated the role of Pax6, a gene that regulates early eye development, in retinal stem cells.1 Residing in the ciliary epithelium of the eye, retinal stem cells are multipotent cells that can differentiate into every retinal cell type.2 After completing her MSc, she spent a few months at Dalhousie University to study model systems in stem cell biology, and subsequently pursued her PhD at Arizona State University, which had just launched a new graduate program in Biology and Society.

Dr. Sunderland praises the PhD program, as it allowed her to study both the scientific and cultural complexities of stem cells. Through her dissertation, which focused on the history of regenerative medicine, she had the opportunity to work with many leading figures in the field. After completing her doctorate research, Dr. Sunderland pursued a post-doctoral fellowship at the Berkeley Center for Science, Technology, Medicine and Society, University of California (Berkeley), where she explored the ethical and practical implications of conducting research with a specific translational aim. Through her projects, Dr. Sunderland published and co-authored multiple papers to evaluate how the emerging ethos of translational research acts as a powerful determinant in funding for biomedical sciences. Her work focused on three topics: how social, political, and cultural contexts can limit promising research; the importance of strategically funding research and developing innovative regulatory policies; and the necessity to mobilizing patient advocates. Following her work at Berkeley, Dr. Sunderland decided to retire the laboratory component of her research in favor of embracing her passion for science communication and translational research; a field she was very interested in as a graduate student. She studied translational research for a decade, and, bringing forth her background in retinal stem cells, Dr. Sunderland was thrilled to become FFB’s Director of Research and Education. At FFB, she oversees the translational research portfolio and complementary educational program; both of which aim to drive the development of new treatments for eye disease causing blindness. When asked to describe her typical day, she said, “There is none—I might be designing a new research funding opportunity, speaking with patients at a community vision health event, or advocating for better access to genetic testing.”

Although there are currently no stem cell clinical trials for treating eye diseases causing blindness in Canada, Dr. Sunderland believes it has been an exciting year for stem cell clinical trials nonetheless. Her optimism is based on the number of promising, albeit contradictory, experimental stem cell trials carried out internationally. Notably, Dr. Masayo Takahashi from the RIKEN Institute in Japan, through her publication in the New England Journal of Medicine, described the first successful stem cell transplantation that used induced pluripotent stem cells from another donor as an experimental treatment for an eye disease causing blindness called age-related macular degeneration.3 However, in the same issue, another publication reported that three women became blind after participating in a clinical trial that uses stem cells derived from patient’s own adipose tissue to treat blindness.4 When asked about these unfortunate results, Dr. Ajay Kuriyan, who is the first author of the paper, noted that the technique is widely being used in commercial stem cell clinics. Furthermore, despite the negative data, Dr. Kuriyan indicated that pre-clinical data exists regarding the ability of these stem cells to differentiate into the retinal pigment epithelial or photoreceptor cells and restore vision.

Amidst these conflicting results, Dr. Sunderland has focused her efforts on increasing public awareness about blindness, and the relevant current clinical trials and stem cell tourism industry, through her public lectures, and her engagement in public discourse via blogging (FFB blog and Twitter (@FFB_Research; and @SciParty; a science chat forum hosted every Friday at 1pm). For example, while many researchers were successfully able to treat degenerative eye diseases in animal models using photoreceptors and retinal pigmented epithelium derived from Embryonic Stem Cells (ESCs) and Induced Pluripotent Stem Cells (iPS) cells, laboratories in the United Kingdom, Japan, and United States have not attained successful results through human clinical trials. Juxtaposing these two findings highlights both the excitement and great challenges that lie ahead in the research for treating blindness. Evidently, a key barrier to patients is in judging the credibility of clinical trials, which prompted Dr. Sunderland to recommend FFB as a trusted source of information about emerging treatments and clinical trials. And while there is a tremendous potential for stem cell research to treat eye diseases causing blinding, it is tempered by the risk that a dangerous trial can hinder the credibility of the field for decades.

Finally, she advises young researchers and graduate students to keep reading—“One of my favorite things about being in graduate school was reading. I’ve always loved reading, so it was a true privilege to take a deep dive into so many important texts, and then, it was even better to discuss these new ideas with peers, teachers, and mentors.” Also, “This is what’s great about being a student: it’s your job to always be learning. I think I will always be a student at heart.”

 

References

  1. Xu S, Sunderland ME, van der Kooy D, et al. The proliferation and expansion of retinal stem cells require functional Pax6. Developmental Biology. 2007; 304: 713–721.
  2. Tropepe V, Coles BL, Chiasson, BJ, et al. Retinal stem cells in the adult mammalian eye. Science; 2000; 287, 2032–2036.
  3. Mandai M, Fujii M, Takahashi M, et al. Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration. N Engl J Med; 2017; 376:1038-1046.
  4. Kuriyan AE, Albini TA, Goldberg JL, et al.Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMDN Engl J Med; 2017; 376 (11): 1047.
  5. Nommiste B, Fynes K, Coffey P, et al. Stem cell-derived retinal pigment epithelium transplantation for treatment of retinal disease. Prog Brain Res; 2017; 231:225-244.