Professor Alberto Auricchio’s research project on Gene therapy of Stargardt disease with AAV intein vectors was chosen as the winner of the € 100,00 Arrigo Recordati Prize 2019. Alberto Auricchio, MD is Professor of Medical Genetics at the Department of Advanced Biomedicine, “Federico II” University in Naples, and Coordinator of the Molecular Therapy Program at Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli (Naples), Italy. His research is focused on gene therapy of retinal and metabolic diseases using adeno- associated viral vectors.
Alberto Auricchio, M.D.
Telethon Institute of Genetics and Medicine
(TIGEM), Naples, Italy
2019 Award Winner
Alberto Auricchio, MD is Professor of Medical Genetics at the Department of Advanced Biomedicine, “Federico II” University in Naples, and Coordinator of the Molecular Therapy Program at Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli (Naples), Italy. His research is focused on gene therapy of retinal and metabolic diseases using adeno-associated viral vectors. His group has contributed to the phase I/II clinical trial of Luxturna, the first approved gene therapy drug for an ocular disease, and to the development of gene therapy for mucopolysaccharidosis VI up to an ongoing phase I/II trial.
Professor Auricchio is co-author of more than 130 peer-reviewed publications on international scientific journals and inventor of several international patents on the use of viral vectors for gene therapy. He is a member of the editorial boards of various journals and of the European Society of Cell and Gene Therapy.
In 2006 Professor Auricchio received the Outstanding New Investigator Award from the American Society of Gene Therapy and in 2007 was nominated “Cavaliere of the Italian Republic” by the President of the Italian Republic. In 2011 Professor Auricchio received the Consolidator Grant from the European Research Council - ERC - and the Advanced Grant in 2016.
Gene therapy of Stargardt disease
with AAV intein vectors
Alberto Auricchio, M.D.
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
Our group has a long-standing interest in the development of gene therapies for inherited ocular diseases. Our research spans from tailoring the adeno-associated viral (AAV) vector platform to retinal gene transfer to proof-of-concept in animal models of retinal disease up to first-in-human. Indeed, we have importantly contributed to the phase I/II clinical trial of Luxturna, which is the first ocular gene therapy product on the market.
One of the limitations of AAV is its DNA cargo capacity of about 5 kb in size. This would not be sufficient for gene therapy of conditions like Stargardt disease (STGD1), the most common inherited macular degeneration in humans, which is caused by mutations in ABCA4, a gene with a coding sequence significantly larger than 5 kb.
To overcome this, we have recently developed a system based on two AAV vectors, each encoding for one of the two halves of ABCA4 each flanked by short split-inteins which mediate protein trans-splicing and full length ABCA4 reconstitution in the retina of mice, pigs and in human retinal organoids. This system reduces lipofuscin accumulation in a mouse model of STGD1 and supports further development of AAV intein for therapy of STGD1 and other Inherited Retinal Diseases (IRDs) due to mutations in large genes.
The overall objective of the project funded by Arrigo Recordati International Prize for Scientific Research is to translate this proof-of-concept of pre-clinical efficacy of AAV split intein for STGD1 into a first-in-humans by defining both AAV intein dose-response and safety in view of a future clinical trial. This will importantly contribute to the development of gene therapy for the common and severe STGD1.
Icahn School of Medicine at Mount Sinai
Mount Sinai Health System, New York, NY
Robert J. Desnick is Dean for Genetic and Genomic Medicine and Professor and Chairman Emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.
In 1977, he joined the Mount Sinai faculty as the Arthur J. and Nellie Z. Cohen Professor of Pediatrics and Genetics, and Chief of Medical and Molecular Genetics. From 1993- 2011, he was the first Chairman of the Department of Genetics and Genomic Sciences at Mount Sinai. In 2011 he became the Dean for Genetics and Genomic Medicine.
Dr. Desnick’s research interests include lysosomal storage diseases (LSDs) and the inborn errors of heme biosynthesis, the porphyrias, and in particular, their treatment. His research efforts led to the Federal Drugs Administration (FDA) - and European Medicine Agency (EMA) - approval of enzyme replacement therapy (ERT) for Fabry disease (Fabrazyme) and on-going ERT clinical trials (FDA “Breakthrough” status) for Niemann- Pick B disease, both in partnership with Genzyme. In addition, he was a scientific founder of Amicus Therapeutics (NASDAQ; FOLD), which is developing oral pharmacologic chaperone therapy for Fabry disease (EMA-approved in 2016), Pompe disease, and other disorders. Currently, his laboratory is using gene editing technology to engineer gene therapy in the mouse model of Fabry disease with Sangamo Therapeutics.
For the porphyrias, he co-developed with Alnylam Pharmaceuticals an RNAi therapy for the acute hepatic porphyrias, performed the preclinical studies, and co-designed the ongoing clinical trials. He also served as Principal Investigator for Clinuvel Pharmaceuticals’ Phase 2 and 3 multisite clinical trials of afamelanotide, a “first-in-class” synthetic peptide for the treatment of the Erythropoietic Porphyrias, which was recently EMA-approved and pending FDA approval. He also served as the Chairman of the Scientific Advisory Committee (SAC) of Synageva Biopharma and currently serves as SAC Chair for Kiniksa Pharmaceuticals. In addition, his research includes genomics, pharmacogenomics, and personalized medicine. He has published over 740 research papers and chapters, including nine edited books. He is an elected Fellow of the American Association for the Advancement of Science and an elected member of the National Academy of Medicine.
Robert J. Desnick
Director of the Division of Pediatric Nephrology
Chief of the Department of Pediatric
Subspecialties, IRCCS Children’s Hospital
Bambino Gesù, Rome, Italy
Francesco Emma received his medical degree from the Catholic University of Louvain, Brussels, Belgium, where he specialized in Pediatrics. He subsequently completed his training in Pediatric Nephrology at Boston Children’s Hospital, Harvard Medical School,
and moved to the Bambino Gesù Children’s Hospital in Rome as a staff member in the Division of Nephrology and Dialysis. There, he served as the Head of the Rare Kidney Disease Clinic before being appointed Head of the Pediatric Nephrology Division in 2005, and has set-up the Nephrology Research Laboratory. He currently holds the position of Head of the Department of Pediatric Subspecialties.
Dr. Emma’s primary research interests lie in rare renal diseases, in particular in cystinosis and nephrotic syndrome. He has authored more than 160 research articles in peerreviewe journals and is the author of several textbook chapters. He has also served in the editorial board of several scientific journals, including Pediatric Nephrology, the Journal of Nephrology and Nephrology Dialysis and Transplantation. He is an editor for the textbook “Pediatric Nephrology”.
Among his other appointments, he is the current chair of the Working Group on Inherited Renal Disorders of the European Society of Pediatric Nephrology (ESPN), has been pastsecretary of the Working Group on Inherited Kidney diseases of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), the past Chair of the Teaching Course Committee of the International Society of Pediatric Nephrology and the past-President of the Italian Society of Pediatric Nephrology.
Child Healthcare and Genetic Science
Laboratory, Division of Health Science,
Osaka University, Japan
Norio Sakai is a Professor at the Osaka University Graduate School of Medicine, in the Child Healthcare and Genetic Science Laboratory of the Health Science Division, in Osaka. Dr. Sakai graduated from the Department of Astronomy at Tokyo University in 1982 and the Osaka University Graduate School of Medicine in 1987. He completed his clinical training as a residency in 1990. He received a Ph.D from the Osaka University Graduate School of Medicine in 1994 with a paper on molecular cloning for Krabbe disease (Krabbe disease: Isolation and characterization of a full-length cDNA for human galactocerebrosidase).
He worked as a Research Fellow in the Department of Environmental Medicine, Res. Inst. Osaka Medical Center for Maternal and Child Health, Osaka for two years and moved to GSF-Institute for Mammalian Genetics in Germany. He returned to Japan in 1998 to the Department of Paediatrics at the Osaka University School of Medicine and was appointed to the position of Assistant Professor in 2005, later working as Associate Professor from 2009. He led the clinical and research group for inborn errors of metabolic disease and medical genetics in the Pediatrics Department.
Dr. Sakai has published more than 60 articles in peer-reviewed international journals and has received several awards for his research on molecular analysis for inborn errors of metabolic diseases. His clinical work focuses on the clinical treatment of lysosomal diseases with advanced methods including enzyme replacement therapy and hematopoietic cell transplantation. His more recent research has focused on disclosing the basic molecular pathology of lysosomal diseases and developing new treatments including chaperone therapy.