Introduction
The urgent mission of the Foundation Fighting Blindness is to support the development of treatments and cures for inherited retinal dystrophies. Gene therapy is emerging as a leading therapeutic approach for these predominantly monogenic diseases, especially following the December 2017 FDA approval of LUXTURNA® for the treatment of retinal diseases caused by biallelic pathogenic variants in the RPE65 gene. However, while gene therapy is very promising, both preclinical and clinical data indicate it stimulates the immune system and in doing so may be limiting optimal dosing and efficacy while also impacting clinical practice and study design.
The Virtual Workshop on Inflammation in Viral Gene Therapy of the Retina, September 14-15, 2020 was designed to bring together industry and academia to discuss openly what is known about the interactions of viral-mediated gene therapy of the retina with the immune system and the clinical consequences of that. The meeting was by invitation only, to keep the group small enough to promote robust discussion.
The organizers of the Workshop were immunologists Dr. Thomas Langmann, University of Cologne; Dr. Andrew Dick, University College London; Dr. Kai Chan, Harvard; along with regulatory consultant Dr. Curt Scribner, industry representative Ms. Sara Mary Hall, Ocquila; and the Foundation chief scientific officer Dr. Brian Mansfield. Regulatory consultant Dr. Joy Cavagnaro was an invited moderator.
Workshop Goals
- Understand the current state of knowledge of intraocular immunologic functions
- Understand the current knowledge of immune activation in inherited retinal diseased eyes prior to treatment
- Understand the mechanisms causing the non-clinical and clinical immune responses observed in ocular viral gene therapy
- Understand the limitations that immune responses place on optimizing outcomes
- Identify critical knowledge gaps the Foundation may be able to direct research funding towards
- Publicly disseminate a summary of the Workshop and its outcomes
Prior to Meeting Assignment
To ensure everyone started with the same core information about immunology and the processes that were to be discussed during the workshop, we asked all attendees to watch the following pre-recorded presentations:
Virtual Workshop Survey
A pre-meeting survey on preclinical and clinical experience with inflammation in viral gene therapy of the retina was circulated ahead of the meeting and a summary of the survey results is provided below.
Virtual Workshop Agenda
Day 1 – Monday, September 14, 2020
Iceberg of Inflammation: Preclinical data - should we worry?
Overview of the Day
- How preclinical models develop our understanding:
- What is extent of inflammation and immune activation?
- What protocols are being used to control inflammation?
- Do animal models inform appropriately?
- Modifications of vector, capsid and transgene to reduce inflammation
Day 2 – Tuesday, September 15, 2020
Clinical Inflammation: What we know and contemporary clinical data
Clinical Research
This session will be a discussion of preclinical and clinical data for gene therapies that have been, or still are, in the clinic. The presentations should focus on:
- Preclinical data that led to dose decisions and toxicology of concern
- Data that led to immunosuppression protocol
- Data on immune responses observed
- Data on clinical inflammation observed
Workshop Attendees
Gustavo Aguirre, VMD, PhD
Gustavo is Professor of Medical Genetics and Ophthalmology at PENN's School of Veterinary Medicine, and works with dog models of inherited eye and retinal disease. He earned all his degrees at PENN, where he also completed a residency in ophthalmology before serving as a post-doctoral fellow at Hopkins' Wilmer Institute. He joined Penn in 1973 as assistant professor, left as professor for Cornell in 1992, and returned to PENN as professor in 2004. He has received many awards including the Alcon Award and ARVO's Proctor medal, and is an elected member of the National Academy of Medicine and a fellow of AAAS.
William Beltran, DVM, PhD, DECVO
Dr. Beltran is a Professor of Ophthalmology at the School of Veterinary Medicine of the University of Pennsylvania where he practices clinical veterinary ophthalmology and heads a research laboratory focused on inherited retinal degenerative diseases and the development of novel therapeutic strategies. Ongoing projects in his group are aimed at characterizing the link between mutation and photoreceptor cell death, and developing novel treatment modalities such as corrective gene therapy, neuroprotection, the use of optogenetic/optochemical tools for vision restoration, and stem cell therapies to replace photoreceptor cells. His work using canine models of IRDs has led to the development of gene therapies for RPGR-XLRP, RHO-ADRP, and NPHP5-LCA.
Dr. Beltran is also the Director of PennVet’s Division of Experimental Retinal Therapies (www.vet.upenn.edu/ExpeRTs), a unique consortium of veterinary ophthalmologists and vision scientists whose mission is to facilitate the development, screening, and testing of novel retinal therapies that rescue or restore vision in people and animals through collaborations with academia and industry.
Jean Bennett, MD, PhD
Director, Center for Advanced Retinal and Ocular Therapeutics (CAROT), University of Pennsylvania Perelman School of Medicine
Professor of Ophthalmology; Cell & Developmental Biology, University of Pennsylvania Perelman School of Medicine
Jean Bennett is a physician-scientist with experience/expertise in molecular biology, vector development and gene therapy translational studies. Dr. Bennett has established a true “from bench to bedside” program, and thus she is familiar with steps necessary to go from proof-of-concept all the way to those necessary for testing of safety and efficacy in humans with blinding disease. Dr. Bennett was the scientific leader of a team that translated reversal of blindness in animal models to demonstration of efficacy and safety in children and adults. Her team was the first to enroll pediatric subjects with a non-lethal disease as gene therapy participants. The team completed both a re-administration study and, with Spark Therapeutics (of which she is a scientific founder), a Phase 3 registration gene therapy trial for congenital blindness, the first randomized, controlled, multi-center gene therapy Phase 3 gene therapy trial targeting a genetic disease. This work led to the first approved gene therapy for inherited disease in USA (2017) and in Europe (2018) and more recently in the UAE (2019). This is also the first approved gene therapy product targeting a retinal disease worldwide. Through her Center, the Center for Advanced Retinal and Ocular Therapeutics (CAROT) at the University of Pennsylvania, Dr. Bennett continues to develop gene-based therapies for other retinal degenerative diseases and to tackle some of the limitations of current gene therapy technologies. She mentors scientists and physicians at all career stages, serves on a number of advisory panels, and is an active member of non-profit patient-oriented foundations.
Shannon Boye, PhD
Dr. Shannon E. Boye is an Associate Professor and Associate Chief of the Division of Cellular and Molecular Therapy in the University of Florida’s Department of Pediatrics. She received her BS in marine biology with a minor in chemistry from Fairleigh Dickinson University in 2001. She graduated with a PhD in Neuroscience from the University of Florida in 2006. Her thesis work involved developing viral vectors for the treatment of retinal disease, specifically GUCY2D Leber Congenital Amaurosis (LCA1). Following a postdoctoral fellowship and research assistant professorship Dr. Boye was appointed as tenure track Assistant Professor in the University of Florida’s Department of Ophthalmology (2012). In 2016, she received tenure and was promoted to the rank of Associate Professor. In 2020, she transferred to the Department of Pediatrics where she is now Associate Chief of the Division of Cellular and Molecular Therapy.
Dr. Boye has authored over 50 peer-reviewed manuscripts, multiple textbook chapters, is actively involved in grant and manuscript review, and is the recipient of several major awards including the ARVO Foundation/Merck Innovative Ophthalmology Research Award in Gene Therapy and Eye Disease, the Foundation Fighting Blindness Board of Director’s Award, the ARVO Foundation/Pfizer Ophthalmics Carl Camras Translational Research Award, a University of Florida Research Foundation Professorship, and the Gund Harrington Scholar Award for excellence in gene therapy research. She is co-founder and Chief Scientific Officer of Atsena Therapeutics, a clinical-stage start up company focused on developing gene therapies for inherited retinal disease and optimizing AAV vectors for safe and efficient gene delivery to patient retinas.
Joy Cavagnaro, PhD, DABT, Fellow ATS
Joy Cavagnaro, PhD, DABT, Fellow ATS, is the President of Access BIO where she consults on science-based development strategies for novel drug, biologics and device combinations. Her career spans academia, the CRO and biotechnology industries and government. During her tenure at CBER/FDA she was appointed to the SBRS and served as FDA’s safety topic lead and rapporteur for “ICH S6.” She was the first to advocate the “case-by-case” rational science-based approach to preclinical safety evaluation. In 2011 she received SOT’s Biotechnology Specialty Section First Career Achievement Award and in 2019 the Society’s Arnold J. Lehman Award which recognizes individuals who have made significant contributions to risk assessment and/or the regulation of chemical agents, including pharmaceuticals. She is Founder and Past Chair of the leadership committee of BioSafe, an expert preclinical science committee within BIO. She is a Past Chair of the Clinical and Regulatory Affairs Committee and Translational Science & Product Development Committee of the ASGCT. She was a member of the NTP Scientific Advisory Committee on Alternative Toxicological Methods and is currently an advisor and member of the Grants Working Group of the California Institute of Regenerative Medicine. She serves on multiple SAB’s including Odylia Therapeutics a non-profit corporation devoted to moving ultra-rare inherited retinal diseases ‘from science to humans’. Dr. Cavagnaro consults and lectures internationally on translation and risk assessment of novel therapies. She has co-authored numerous white papers and chapters related to various aspects of preclinical safety assessment. The book she edited “Preclinical Safety Evaluation of Biopharmaceuticals A Science-Based Approach to Facilitating Clinical Trials” published by John Wiley & Sons, NJ, 2008, commonly referred to as the “BioBible”.
Connie Cepko, PhD
Connie Cepko is Bullard Professor of Genetics and Neuroscience at Harvard Medical School and a Howard Hughes Medical Institute Investigator. She trained in virology with Phil Sharp at MIT for a Ph.D. and later with Richard Mulligan at the MIT Whitehead Institute. She helped develop retroviral vectors for transduction into the nervous system for lineage analysis and for studies of gene function in vivo. Her laboratory has focused on the topic of cell fate determination in the retina through the analysis of the behavior of progenitor and stem cells. More recently, they have been studying the mechanisms of photoreceptor death in diseases that cause blindness, such as retinitus pigmentosa and macular degeneration.
Kai Chan, PhD
Ying Kai Chan is Co-Founder of Ally Therapeutics, a venture-backed gene therapy company, and Visiting Scholar at Harvard Medical School. Previously, he served as junior faculty at Harvard University. He performed postdoctoral research at Harvard Medical School, where he also received a Ph.D. in Microbiology and Immunobiology and a certificate in Human Biology and Translational Medicine. His research interests are at the interface of viruses and the human immune system, with a focus on molecular engineering of desired viral and immune functions. He is currently exploring innovative technologies to modulate inflammatory responses to AAV gene therapy.
Janet Cheetham, PhD
Janet has more than 30 years of industry experience in drug development. She currently consults for start-up companies to plan/execute INDs, and phase 1-3 studies. She also consults with a non-profit company in rare disease with a network of study sites for natural history studies. Janet’s last position at Allergan was Vice President, Clinical Development in the Retina Therapeutic Area. She was the project team leader and clinical lead for several compounds from pre-IND to market launch and was responsible for external collaborations and internal programs. Janet also served as Vice President of Clinical Operations for about 5 years. Janet earned her Doctor of Pharmacy from University of Southern California and completed a post-doc fellowship at Doheny Eye Institute in Los Angeles in conjunction with the University of Southern California.
Andrew Dick, MD
Andrew D Dick FMedSci
Director UCL-Institute of Ophthalmology, Duke Elder Professor of Ophthalmology, UCL Institute of Ophthalmology. London, UK, Professor of Ophthalmology, University of Bristol, UK
Faculty and Theme Lead for Inflammation and Immunotherapeutics of National Health Institute for Research Biomedical Research Centre, Moorfields Eye Hospital and UCL-Institute of Ophthalmology, London.
Professor Andrew Dick qualified in medicine also with a degree in Biochemistry (BSc (Hons)) from the University of London, and during his medical education he spent time as an MRC sponsored research associate in Biochemistry with Professor Coleman in Yale. Following training in internal medicine and MRCP he entered ophthalmology residency and obtained his postgraduate research degree, MD in Immunology in 1993 at the University of Aberdeen with Professor John Forrester. He underwent an MRC Post Doctoral Travelling Fellowship to work with Jon Sedgwick at the Centenary Institute of Cancer Medicine and Cell Biology in Sydney Australia. His clinical expertise is in inflammatory disorders of the eye.
His research spans the basic and translational science conduit to early phase trials in inflammation as related to autoinflammatory, autoimmune and degenerative retinal disease, as well as randomized control trials for immunomodulatory therapy in uveitis. Professor Dick was made a Fellow of the Academy of Medical Sciences (UK) in 2007 for his significant contribution to research and scholarship in medicine and was awarded the Alcon Research Institute Research annual award in 2011.
Prior to becoming Director of Europe’s largest Vision Science and Ophthalmology centre, the UCL-Institute of Ophthalmology, he was Director of Research for the Faculty of Medicine and Dentistry at University of Bristol. He has previously been Editor of British Journal of Ophthalmology, President of European Vision and Eye Research (EVER), Master of Oxford Ophthalmological Congress and vice-president of ARVO.
Jacque Duncan, MD
Dr. Duncan has over 20 years of experience treating and characterizing patients with retinal degenerations. Her faculty career began with K08 funding to work with Matt LaVail, PhD, characterizing novel models of retinal degeneration. Over the past 15 years she has worked closely in collaboration with Austin Roorda, PhD, to characterize cone structure non-invasively in living eyes of patients with a variety of retinal diseases using adaptive optics scanning laser ophthalmoscopy (AOSLO). They have developed improved strategies to quantify cone photoreceptor integrity in normal eyes and eyes with retinal degeneration. She has worked collaboratively with co-investigators to describe the clinical phenotype of patients with genetic mutations that cause retinal degeneration, and to develop novel outcome measures for monitoring disease progression in patients with retinal degenerations.
As a translational clinician-scientist and Director of the Retinal Degenerations Clinic and Retinal Electrophysiology Laboratory at the University of California, San Francisco (UCSF), Dr. Duncan has expertise in the diagnosis and management of patients with retinal degenerations. The Retinal Degenerations Clinic at UCSF serves as a referral center for patients with retinal degenerations for all of northern California with a database of over 1,500 patients. Dr. Duncan has participated in numerous clinical trials including trials of CNTF, the Argus 2 system and the Acucela SeaStar study. She has served on the Data Safety Monitoring Committee for numerous trials of gene augmentation in retinal degenerations including choroideremia, X-linked retinoschisis, achromatopsia and Usher syndrome type 2A.
Dr. Duncan also serves as Chair of the FFB Scientific Advisory Board Chair and Executive Committee Chair for the FFB Clinical Consortium. She leads the Consortium RUSH2A studying the rate of progression in USH2A-related retinal degeneration.
Todd Durham, MS, PhD
Vice President, Clinical & Outcomes Research, Foundation Fighting Blindness
Raleigh, NC
Todd Durham is the Vice President, Clinical & Outcomes Research at the Foundation Fighting Blindness, a national non-profit that funds research to treat and cure inherited retinal diseases. In his current role, Todd is responsible for directing the Foundation’s Clinical Consortium of retinal experts, developing strategies to enhance product development, partnering with industry, and providing technical input on partnered programs and investment decisions. Todd has over 25 years of drug development experience. Prior to his current position, he contributed to research on numerous marketed products as Director of Biostatistics with IQVIA’s Real World Evidence Solutions, was a doctoral fellow with Bristol Myers Squibb, and worked in various statistical and leadership roles for Novan, Inspire Pharmaceuticals, Quintiles, and as a self-employed consultant. Todd earned a BSPH and MS in biostatistics and a PhD in health policy and management (Decision Science and Outcomes Research) from the UNC Gillings School of Global Public Health.
Karen Elkins, PhD
Dr. Karen Elkins obtained a B.A. in Chemistry from Wake Forest University in 1977, followed by a Ph.D. in Microbiology and Immunology at Duke University in 1982, postdoctoral training at USUHS and NIH, and most recently an M.A. in Science Writing at Johns Hopkins University in 2019. Since 1993, she has been a Senior Investigator and Supervisory Research Biologist at the Center for Biologics Evaluation and Research (CBER) of the U.S. FDA, also known as a “Researcher/Reviewer.” In that capacity, she directs a research group devoted to understanding protective immunity against intracellular bacteria such as Mycobacterium tuberculosis and Francisella tularensis, and she reviews new bacterial vaccines proposed for clinical trials under U.S. IND. Dr. Elkins, recognized as an international expert in infectious disease immunology, is appointed to the U.S. Senior Biomedical Research Service (SBRS) of the U.S. government, and often serves as a meeting organizer, speaker, and expert reviewer. In addition to her subject matter expertise, she has long-standing interests in scientific professional practices and science communication, and now also works as a freelance science writer.
Scott Ellis, PhD
Scott graduated from University College London in 1999 with a PhD in Genetics and moved to the Brunel Institute for Cancer Genetics and Pharmacogenomics at Brunel University (London) where he conducted postdoctoral research in the identification of tumour suppressor genes. In 2002 he moved to the Wellcome Trust Centre for Human Genetics in Oxford to work on the genetics of heart disease. He joined Oxford BioMedica in 2006 to start an 11 year career in gene and cell therapy Product Development and was ultimately responsible for the R&D of the Company’s product pipeline as Head of Early Development. During this time he saw preclinical programmes progress into the clinic for chronic ocular conditions such as wet age-related macular degeneration, Stargardt disease and Usher syndrome. Scott moved to Gyroscope Therapeutics in 2017 where he is responsible for the development of both the early pipeline programmes and platform technologies as VP Preclinical Research. Gyroscope treated its first patient with GT005, its lead programme for dry AMD, at the start of 2019 and has recently initiated the Phase II study.
Dominick Fischer, MD, DPhil, FEBO
Professor M Dominik Fischer MD DPhil FEBO is a Consultant Ophthalmic Surgeon at the Oxford Eye Hospital, in Oxford, UK. He specializes in retinal diseases and their treatment. After receiving his medical doctorate (summa cum laude) for research performed as Visiting Scholar at the University of Pennsylvania, he trained with Professor Bartz-Schmidt and Eberhart Zrenner and became registered specialist and Fellow of the European Board of Ophthalmology in 2012. He continued his training at Oxford, reading Clinical Neuroscience at Merton College as MRC Clinical Research Fellow and received his second doctorate for developing a new form of retinal gene therapy.
He was appointed Professor of Ophthalmology at the Centre for Ophthalmology Tübingen in 2015, where he still holds an appointment as Consultant Ophthalmic Surgeon and Principal Investigator. His academic work focuses on translational research in retinal physiology and disease (http://www.eye-tuebingen.de/fischerlab/). He leads several clinical trials and is Chief Investigator of the first global post approval safety study for ocular gene therapy.
John Flannery, PhD
John G. Flannery, PhD has been a faculty member in the Department of Molecular and Cell Biology, University of California, Berkley, since 1995 and is currently the Professor of Vision Science and Neuroscience at the University of California, Berkeley. His research program is focused on understanding the genetic and biochemical underpinnings of inherited retinal degenerations and designing genetic therapies for these blinding conditions. The expertise of his laboratory group is directed toward developing viral vectors for gene therapy and gene transfer to retinal neurons, epithelia, and glia. His team have developed small animal models of retinal degenerations and treatments for these conditions for over 30 years. He studies both normal retinal functions as well as disease states to develop rational therapeutics for retinal dystrophies. He has over 2 decades of expertise in promoter design and AAV serotype selection and modification to generate viral vectors that can efficiently transfect retinal cells, in vivo. He has expertise in analyzing the use of these vectors in animal retina in vivo. In his studies to develop viral vectors targeted to specific classes of retinal neurons, he uses ‘directed evolution’ approaches to identify capsid variants as well as promoter selection to optimize cell class-specific expression and minimize off‐target ectopic expression. He has experience in expression functional indicators of neuronal activity, e.g. genetically‐encoded calcium indicators (gCamP) as well as optically switched receptors and ion channels (Chr2, and LiGluR). In parallel, to his gene-specific inherited retinal disease therapies, he has also developed optogenetic gene therapy. Flannery is a cofounder ofVedere Bio Inc, a startup biotech company that is developing gene therapy products to restore functional vision to patients who have inherited retinal degenerations, and other causes of vision loss.
Sara Mary Hall
A scientist by training with over twenty-five years’ gene therapy experience in the US, Europe, Japan, and Australia, Sara is the Chief Executive Officer of OcQuila Therapeutics and has co-founded and led four private and led a fifth, public biotech. She serves on the Board of Directors of University of Kansas Center for Technology Commercialization and is a member of the Australian Regenerative Medicine Institute (ARMI) Industry Advisory Committee. A member of the Kansas chapter of the International Women’s Forum, Sara has been involved in national and international initiatives for women and girls in the sciences, and is a semi-professional violinist performing with the Bainbridge Symphony Orchestra, Port Townsend Symphony, and Bridges: A String Ensemble. The winner of two R&D 100 awards for scientific innovation while still at the bench, Sara is a creative, experienced, and driven executive with a specialty in and passion for first-in-class products and concepts.
Chad Jackson, PhD
Dr. Chad R. Jackson is committed to transforming ideas and projects addressing inherited retinal degenerations into clinical solutions. Currently, he oversees the Foundation Fighting Blindness’ preclinical translational research programs providing subject matter expertise and dedicated program management. Dr. Jackson has over 20 years of research and development experience in biomedical sciences and is a champion for international science engagement, innovation ecosystem development, and entrepreneurship as a means to problem solving and economic development.
Prior to joining the Foundation, Dr. Jackson supported the Defense Advanced Research Projects Agency’s Biological Technologies Office covering topics that span infectious disease, synthetic biology, and human performance. Also, he managed the Laboratory University Collaboration Initiative for Office of the Secretary of Defense’s Basic Research Office and served as a senior science advisor to the Defense Threat Reduction Agency’s Advanced and Emerging Threat Division. In 2014, Dr. Jackson joined the U.S. Department of State as the Emerging Technologies and Innovation Officer for the Science and Technology Advisor to the Secretary of State where he tracked emerging and transformational technologies impacting political and economic landscapes.
Christine Kay, MD
Christine Kay, M.D. is a vitreoretinal surgeon and the director of electrophysiology, retinal genetics, and clinical trials at Vitreoretinal Associates in Gainesville, Florida, and an affiliate assistant professor at the University of South Florida. Prior to this, she was an Assistant Professor and director of the retinal genetics service at the University of Florida. She graduated from Harvard University with a magna cum laude in neuroscience, went to medical school at the University of Florida, and completed her vitreoretinal surgical fellowship at the University of Iowa. After her vitreoretinal surgical fellowship, she was awarded a 5-year Career Development Award from the Foundation Fighting Blindness which launched her career as a clinical-scientist and IRD specialist, and funded research focusing on optimizing AAV genetic therapy for the treatment of achromatopsia. She has developed a large IRD patient population in her clinic, with over 1000 patients in her clinical database and with 800 of these patients genotyped.
Dr. Kay is a member of the American Academy of Ophthalmology and has been inducted into Macula Society and Retina Society, and has published over 20 either first or senior author articles in peer-reviewed ophthalmic journals. She has been an invited speaker at the annual Foundation Fighting Blindness VISIONS conference for the past 6 years, is actively involved in FFB’s clinical trial consortium for inherited retinal disease, and is the senior and organizing faculty on instructional courses on gene therapy annually at ASRS and AAO. She is currently a principal investigator in 12 IRD clinical trials including surgical gene therapy trials and has performed multiple subretinal injections within ocular gene therapy clinical trials. She also serves as clinical ophthalmology advisor for Atsena Therapeutics. Her combined interests in management of IRDs, IRD clinical trials with a particular focus in gene therapy, and optimization of vitreoretinal surgical delivery techniques allows a unique perspective in the field of retinal gene therapy.
Thomas Langmann, PhD
Prof. Thomas Langmann is the chair for Experimental Immunology of the Eye at the Medical Faculty and University Hospital in Cologne, Germany. He studied Biology and received a PhD at the University of Regensburg, Germany. After his postdoc in Boston, he became Principal Investigator of the German Research Council (DFG) group FOR1075 (Cellular Homeostasis of Visual Function). He was appointed as associate professor (W2) in 2010 and full professor (W3) in 2012. He is now vice-speaker of the DFG-Research group FOR2240 “(Lymph)angiogenesis and cellular immunity in inflammatory diseases of the eye”, University of Cologne. His main research interest is cellular innate immunity in retinal degenerative diseases, including the role of microglia in age-related macular degeneration and rare inherited retinal dystrophies.
Amy Laster, PhD
VP Science and Grants, Foundation Fighting Blindness
Amy Laster is the Vice President Science and Grants at the Foundation Fighting Blindness and oversees a $20 million research portfolio consisting of research awards in four funding programs supporting career development, laboratory-based science research, translational research and multi-investigator program projects. In this role, Amy has fostered partnerships with other biomedical research funders to expand the Foundation’s career development program as well as its translational research program. Following the expansion of these programs, Amy has assisted the Foundation’s Development staff to secure major donors to ensure their success and longevity. Additionally, she strategically designs the science programming for several of the Foundation’s national and international conferences.
Prior to joining the Foundation, Amy was a faculty member of the Department of Biology at Stevenson University. She completed a postdoctoral fellowship at Johns Hopkins School of Medicine in the Solomon Synder Department of Neuroscience. Her area of research focus was the study of neurodegenerative diseases, specifically understanding the neurobiology of the autism spectrum disorder, Rett Syndrome. Amy holds a B.S. Natural Science from Spelman College, Atlanta, GA and a Ph.D. Biological Sciences from Purdue University, West Lafayette, IN.
Ian M. MacDonald, MSc, MD CM
Ian M. MacDonald, MSc, MD CM is an ophthalmologist and clinical geneticist. After beginning his professional career in Ottawa, Canada as an Ontario Ministry of Health Career Scientist, he moved to Alberta in Western Canada where he served 4 terms as Chair of the Department of Ophthalmology and Visual Sciences of the University of Alberta, Edmonton. He was Branch Chief, Ophthalmic Genetics and Visual Function, at the National Eye Institute of NIH for 2 years before returning to Edmonton in 2009.
Dr. MacDonald’s area of clinical and research interest is inherited retinal disorders. With funding from the Canadian Foundation for Innovation, the Canadian Institutes for Health Research, Alberta Innovates-Health Solutions, the Foundation Fighting Blindness Canada, and the Choroideremia Research Foundation, Canada Inc., he led a team that completed the first trial of ocular gene therapy in Canada.
Brian Mansfield, PhD
Brian Mansfield, PhD, Executive Vice President Research, Interim Chief Scientific Officer, Foundation Fighting Blindness.
Brian joined the Foundation in 2011. He is responsible for envisioning and implementing the Foundation’s scientific strategy. Brian works with researchers in academia, biotech, industry, and venture capital to accelerate translational research towards human proof of concept studies. In 2013 he established the My Retina Tracker® Registry, an international, online registry for people with an inherited retinal disease (IRD) and in 2017 launched a genetic testing program which provides people with an IRD a no cost comprehensive gene panel test and genetic counseling, to help identify the genetic cause of their disease. With financial support from industry and other non-profit groups, the program has tested over 8,000 people to date. Prior to joining the Foundation, Brian was the Chief Scientist and Vice President for Research and Development for Correlogic Systems Inc., a Senior Scientist in protein development at Human Genome Sciences Inc., a tenured Professor of Eukaryotic Genetics at Massey University, New Zealand, and a Visiting Professor at Georgetown University, Washington D.C. Brian received an honors degree in physical chemistry from Canterbury University; a PhD in biochemistry from the University of Otago, New Zealand; and postdoctoral training in molecular genetics at the Johns Hopkins University School of Medicine.
For over 25 years Brian has also held a position as an Adjunct Scientist at NICHD, NIH, collaborating with Dr. Janice Chou on research that led to a gene therapy for Glycogen Storage Disease type Ia which was licensed to Ultragenyx (DYX-401) and is currently in phase I/II clinical trials. He has over 85 peer-reviewed publications and holds multiple patents.
Bill Merigan, PhD
Dr. Merigan’s current research interests include understanding the function of retinal ganglion cells (RGCs) in the fovea of normal macaques as well as developing optogenetic and cell-based therapies for restoring vision loss. These projects are complementary, since the quality of restored vision in many vision restoration approaches depends on knowledge of the specialized function of the ganglion cell classes mediating vision and how best to drive them. His expertise comes from years of studying the parallel pathways from the macaque retina to the brain, using visual psychophysics, in which monkeys maintain steady fixation in order that test stimuli can be placed at retinal locations to be tested. Recently, in collaboration with David Williams, he has developed a macaque model for in vivo measurement of the function of RGCs using a calcium indicator inserted into RGCs by intravitreal injection. In some cases, optogenetic agents have also been inserted into the same RGCs in order to examine optogenetic vision restoration. The well-known challenge of these studies is that transgene expression (GFP, G-CaMP, or optogenetics) is typically confined to a narrow annulus around the fovea, apparently a result of the ILM as a barrier to vector penetration. Recently Dr. Merigan has been able to spatially extend the ring of RGC expression substantially by treatment of the monkey with cyclosporine prior to injection.
Juliette McGregor, PhD
Juliette McGregor is a research associate at the Center for Visual Science at Rochester. After undergraduate and graduate studies in Physics and Neurobiology at Cambridge University, UK she pursued interdisciplinary research in imaging and the perception of polarized light that led her to Rochester to work under the mentorship of Bill Merigan and David Williams. Juliette specializes in adaptive optics calcium imaging ophthalmoscopy and has used this technique to record optogenetically restored retinal ganglion cell activity in the living primate eye. Her interests span optogenetic and cell-based therapies with a particular emphasis on optimizing restored vision at the fovea.
Kathryn Pepple, MD, PhD
Kathryn Pepple MD, PhD is an Associate Professor in the Department of Ophthalmology at The University of Washington. She is a clinician scientist and uveitis specialist. Her lab studies ocular immune responses in animal models with a special interest in innate immune function in the mechanism of post-infectious uveitis.
Jose-Alain Sahel, MD
Dr. José-Alain Sahel is a Distinguished Professor and the Eye and Ear Foundation Endowed Chair of the Department of Ophthalmology University of Pittsburgh School of Medicine as well as an Exceptional Class Professor of Ophthalmology at the Sorbonne Université in Paris. He is the Director of the UPMC Eye Center, UPMC. Dr. Sahel received his medical degree from Paris University School of Medicine. He then completed an ophthalmology residency at the A. de Rothschild Ophthalmology Foundation in Paris, and at the Louis Pasteur University Hospital in Strasbourg France, where he also performed a clinical fellowship. He performed a fellowship at Massachusetts Eye and Ear Infirmary, Boston, MA and was a visiting Scholar at Harvard University. He was the Cumberlege Professor of Biomedical Sciences at the Institute of Ophthalmology, University College London. Dr. Sahel founded and still leads the Institut de la Vision in Paris and is a pioneer in the field of vision restoration therapies. He authored over 40 patents and 600 peer-reviewed publications. He co-founded several start-up companies. He is a member of the French and German National Academies of Sciences.
Curt Scribner, MD
Curtis Scribner, MD is an independent regulatory and clinical consultant with a broad experience in cell and gene therapy. He spent 10 years at FDA in CBER after finishing his post-doc at the NIH. Since that time he has worked with many companies in the rare and ultra rare clinical development space, especially in gene therapy applied to the eye.
Mark Shearman, PhD
Chief Scientific Officer, AGTC
Dr. Shearman is responsible for leading AGTC’s product candidate selection process, pre-clinical and translational research and long-term research and development planning, while also contributing to the overall strategic direction of the company. Dr. Shearman has been at AGTC for the last 5 years, and prior to that at EMD Serono, Inc., the U.S. and Canadian subsidiary of Merck KGaA, where he served as Senior Vice-President of Research & Early Development since 2009.
Previously, Dr. Shearman was Executive Director of Merck & Co. Research Laboratories, Boston, and Senior Director at the Merck Sharp & Dohme Research Laboratories Neuroscience Research Centre, U.K. Dr. Shearman earned a B.Sc. (Hons) from the University of Bristol, a Ph.D. from the University of Nottingham and conducted academic research at institutes in Japan and Germany. He has published more than 125 research articles and been involved in the development of 15 clinical drug candidates.
Paul Sieving, MD, PhD
Dr. Sieving is Professor of Ophthalmology and Vision Science, and Director of the Center for Ocular Regenerative Therapy (CORT) at the University of California at Davis. Prior to that he was director of the National Eye Institute, NIH, until 2019. His research focus is on retinal clinical physiology in the inherited retinal dystrophies and mechanisms of vision impairment. He initiated a clinical AAV8-RS1 gene therapy trial for X-linked retinoschisis in 2015. He is a member of the National Academy of Medicine USA and the German National Academy of Sciences.
Tim Stout, PhD
Dr. Stout has been the Sid W. Richardson Professor and Margarett Root Brown Chair of the Department of Ophthalmology, and Director of the Cullen Eye Institute at Baylor College of Medicine since 2013. Prior to that, he served as Professor in the Departments of Ophthalmology and Molecular Genetics, as well as Vice President for Commercialization Strategies at Oregon Health & Science University in Portland, Oregon. He has directed the Clayton Gene Therapy Laboratories since 1995.
Kanmin Xue, PhD
Kanmin Xue is a Wellcome Trust clinician scientist fellow at the University of Oxford and Honorary Consultant Vitreoretinal Surgeon at the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, United Kingdom. His laboratory research focuses on retinal inflammation, degeneration, and development of novel genetic therapies. He previously held the role of National Institute for Health Research (NIHR) Academic Clinical Lecturer in Oxford between 2014 and 2018, leading the retinal gene therapy clinical trials for choroideremia and X-linked retinitis pigmentosa in association with Professor Robert MacLaren. He has completed the UK specialist training in ophthalmology and a vitreoretinal fellowship at the Royal Victorian Eye and Ear Hospital in Melbourne, Australia. He previously conducted PhD research at the MRC Laboratory of Molecular Biology in Cambridge into how DNA editing brings about antibody class switching, underwent clinical training at Trinity College Cambridge, and pre-clinical training at Brasenose College Oxford, where he was awarded Martin Wronker Prize in Medicine.
Ben Yerxa, PhD
CEO, Foundation Fighting Blindness
As its Chief Executive Officer, Dr. Yerxa is responsible for the overall management of the Foundation Fighting Blindness, the world’s leading private funder of research on potential treatments and cures for inherited retinal degenerative diseases including age-related macular degeneration. He also serves as CEO of the Retinal Degeneration Fund, a wholly owned, not-for-profit subsidiary focused on making venture philanthropy investments to further the Foundation’s mission.
Dr. Yerxa has more than 25 years’ experience in biotechnology, drug development, and in translating promising research discoveries into clinical milestones and treatments. His experience, from drug discovery through product launches and in leadership positions, is in the pulmonary, oral health, cardiovascular, HIV, and ophthalmology fields.
Just before joining the Foundation, Dr. Yerxa was president and co-founder of Envisia Therapeutics, a company focused on developing novel ocular sustained delivery therapies for the front and back of the eye.
Dr. Yerxa holds 60 U.S. patents. An inventor of DIQUAS™, an innovative treatment for dry eye approved in Japan, he has been involved in the discovery and development of investigational new drugs, Phase 3 clinical programs, new drug applications, and drug approvals.
Dr. Yerxa earned his PhD in organic chemistry from University of California, Irvine, and BA in chemistry from the University of California, San Diego.
