2019 WORLDSymposium MEETING HIGHLIGHTS
Danilo A. Tagle, PhD, MS received the 2019 Roscoe O. Brady Award for Innovation and Accomplishment
Danilo A. Tagle, PhD, MS, is associate director for special initiatives at NCATS. He also recently served as acting director of the NCATS Office of Grants Management and Scientific Review and currently serves as executive secretary to the NCATS Advisory Council and Cures Acceleration Network Review Board. Prior to NCATS, Tagle was a program director for neurogenetics at the National Institute of Neurological Disorders and Stroke (NINDS), where he was involved in developing programs concerning genomics-based approaches for basic and translational research in inherited brain disorders.
Prior to joining NINDS in 2001, Tagle was an investigator and section head of molecular neurogenetics at the National Human Genome Research Institute and has been involved in the highly collaborative effort toward the positional cloning of genes for Huntington’s disease, ataxia-telangiectasia and Niemann-Pick disease type C. He has served on numerous committees and advisory boards, including the editorial boards of the journals Gene and the International Journal of Biotechnology.
Tagle leverages key resources and expertise through partnerships with stakeholders in biomedical research, including various government agencies, nonprofits, patient advocacy groups, industry organizations, pharmaceutical corporations and others in the private sector. He leads and provides scientific and programmatic oversight and coordination to the following trans-NIH programs:
- Extracellular RNA Communication
- NIH Microphysiological Systems (also known as the Tissue Chip for Drug Screening program)
- Regulatory Science
- Stimulating Peripheral Activity to Relieve Conditions (SPARC)
Tagle obtained his PhD in molecular biology and genetics from Wayne State University School of Medicine in 1990. He was an NIH National Research Service Award postdoctoral fellow in human genetics in the laboratory of Francis S. Collins, MD, PhD, at the University of Michigan. Tagle has authored more than 150 scientific publications and has garnered numerous awards and patents.
Dr. Tagle received the 2019 WORLDSymposium Roscoe O. Brady Award for Innovation and Accomplishment on Tuesday, February 5, 2019 at 7:30 AM.
Mark Dant received the 2019 Patient Advocate Leader (PAL) Award
Each year, WORLDSymposium recognizes one individual for patient advocacy leadership in the field of lysosomal disease. The 2019 Patient Advocate Leader (PAL) award was presented to Mark Dant, the current Chairman of the Board of the Washington DC-based EveryLife Foundation for Rare Diseases, a science-based advocacy organization dedicated to accelerating biotech innovations for rare disease treatments through science-driven public policy. Mark is also the founder and Volunteer Executive Director of the Ryan Foundation and former President and CEO of the National MPS Society.
In 1992, while working as a police officer in the Dallas area, Mark and his wife Jeanne founded The Ryan Foundation with a bake sale after their only child, three-year old Ryan was diagnosed with MPS I. At that time, life expectancy for children with MPS I was less than 15 years. Mark began an immediate global search for scientists and philanthropists who might aid in finding a treatment in time to help children and families living with MPS realize the promise of tomorrow. A conversation with a research scientist at a symposium in Dusseldorf Germany eventually led Mark to Dr. Emil Kakkis, a young researcher at UCLA who was working on a project to help treat MPS, but had little funding. The Ryan Foundation partnered with Dr. Kakkis and provided key funding for his project, which culminated in the development of laronidase, the first and only drug currently approved to treat MPS I. Ryan, now 30 and a graduate of the University of Louisville, is the longest treated person in the world with MPS I. Since the bake sale, the Ryan Foundation has funded millions of dollars in rare disease research.
For the past 25+ years, Mark and the Ryan Foundation have partnered with numerous research scientists and universities to help innovative projects move toward treatment in lysosomal storage disease; to include the essential published laboratory work which provided proof of concept for Intrathecal Enzyme delivery in lysosomal storage disease. Mark and his family have been key advocates speaking to the FDA and in 2009 successfully championed the US House of Representatives to pass the Ryan Dant Health Care Opportunity Act, a bill designed to help those living on Medicaid assistance become gainfully employed. The Dant’s journey has been documented on CBS 60 Minutes, CNN, Biography Magazine, Readers Digest in 13 languages around the world, Golf Digest, the LA Times and numerous newspapers and news outlets across the US.
Mark retired from police work in 2016 as Assistant Chief of Police after serving 32 years as a Patrol Officer, Detective, and Commander leading multiple divisions and Bureaus to include Patrol, Criminal Investigations, Intel, and SWAT. Mark spends his time now volunteering for the EveryLife Foundation, the Ryan Foundation, and numerous other rare disease organizations to help empower the patient advocate through the understanding that all of us have the power to turn action to hope and hope to reality. Mark’s message is that it is not the entity, but the individual who holds the responsibility to make true change.
On Wednesday, February 6, 2019 at 7:30 AM, Mark was presented with the WORLDSymposium 2019 Patient Advocate Leader Award.
CHESTER B. WHITLEY, PHD, MD DELIVERED THE KEYNOTE ON THURSDAY, FEBRUARY 7, 2019
WORLDSymposium was pleased to announce Chester (Chet) B. Whitley, Ph.D., M.D., as the Keynote Speaker for Thursday, February 7, 2019. Dr. Whitley is a tenured Professor in the Department of Pediatrics, the Department of Experimental and Clinical Pharmacology, and Director of the Advanced Therapies Program at the University of Minnesota.
In 1983, Dr. Whitley conducted the first U.S. trials of bone marrow transplantation for Hurler syndrome, other mucopolysaccharidoses, and selected lysosomal diseases including Krabbe disease, Tay-Sachs disease. With the first transplant for Hurler syndrome in the U.S.A. (September 13, 1983, University of Minnesota)1 and the continuing clinical trials during the next decade,2 he characterized the level of response and clinical outcomes. In the case of Hurler syndrome, cognitive testing and imaging showed protection of the brain despite the seemingly impenetrable blood-brain barrier. Being the very first efficacious treatment for a lysosomal disease, this procedure of hematopoietic stem transplant provided the proof-of-principle for development of future enzyme replacement therapies, gene therapy, and other systemic treatments. During these early transplant studies, Dr. Whitley expanded upon the 1960’s “cross-correction” observations at NIH in cultured fibroblasts, and coined the term “metabolic cross-correction”1 and characterized multiple different mechanisms accounting for the clinical responses in patients. In conversation with the U.S.F.D.A. in the early 1990’s, he coined the term “ultra-orphan disease” to differentiate those conditions that are orders of magnitude more rare than the legislated definition of “orphan disease” with prevalence of <200,000.
Dr. Whitley directs the CLIA-certified Gene Therapy and Diagnostics Lab, the first laboratory in North America to offer complete sequencing of a gene to be offered as a ‘clinical diagnostic’ (non-research) test.
In the late 1990s, Dr. Whitley conducted the first clinical trial of gene therapy for a mucopolysaccharidosis condition, Hunter syndrome.3 At that time, he invented4 the DMB dye-binding test for measuring urine glycosaminoglycans (GAG), the most common method for quantifying GAG in diagnostic laboratories globally.
He is also responsible for a number of other ‘firsts’: (a) discovering a ‘pseudo-deficiency’ allele for MPS5,6; (b) finding that combining therapies, e.g., enzyme replacement therapy (ERT) after bone marrow transplantation7 may enhance metabolic correction; (c) demonstrating that small amounts of intravenous laronidase enzyme cross the blood-brain barrier and reduces the pathology in the brain, and improves the learning of mice with Hurler syndrome8; and, recently, that (d) intravenous zinc-finger nuclease gene-editing prevents brain disease in mice with Hurler syndrome9 and Hunter syndrome10.
Dr. Whitley conceived and organized the 1st International Symposium on Mucopolysaccharidosis and Related Diseases (May 20-23, 1988, Minneapolis, Minnesota).11 He is also Director of the Gene Therapy Center at the University of Minnesota supported by an NIH program project grant Gene Therapy for Metabolic Disease for two decades (5P01HD032652).
He is the founding Principal Investigator of the NIH-funded Lysosomal Disease Network currently coordinating 21 clinical studies at 18 institutions. Dr. Whitley is the founding organizer (May 12-15, 2004, Minneapolis, MN USA) and current Course Director of the annual We’re Organizing Research on Lysosomal Diseases scientific meeting ‘WORLDSymposia’ an international forum that fuses basic, translational and clinical research on lysosomal diseases.
On Thursday, February 7, 2019, at 7:30 AM, Dr. Whitley’s Keynote Address The ‘New’ Lysosomal Disease Network, described how the intersection of past lysosomal disease research and current, ongoing, unmet need, has created both the springboard for the next generations of therapies, and provided the overarching vision for researchers and clinicians in the LDN going forward.
- Whitley CB, Ramsay NKC, Kersey JH, Krivit W: Bone marrow transplantation for Hurler syndrome. Assessment of metabolic correction. Birth Defects 22:7-24, 1986.
- Whitley CB, Belani K, Chang PN, Summers CG, Blazar BR, Tsai MY, Latchaw RE, Ramsay NKC, Kersey JH: Long-term outcome of Hurler syndrome following bone marrow transplantation, Am J Med Genet 46:209-218, 1993.
- NIH Recombinant DNA Advisory Committee application; Retroviral-Mediated Transfer of the Iduronate-2-Sulfatase Gene Into Lymphocytes for Treatment of Mild Hunter Syndrome (Mucopolysaccharidosis Type II), Human Gene Therapy Protocol, University of Minnesota Medical School, Minneapolis, MN, Chester B. Whitley, Ph.D., M.D., R. Scott McIvor, Ph.D., Susan A. Berry, M.D., Bruce R. Blazar, M.D., John H. Kersey, M.D., Richard A. King, M.D., Ph.D., Anthony J. Faras, Ph.D., Richard E. Latchaw, M.D., Jeffrey J. McCullough, M.D.,
Norma K.C. Ramsay, M.D.U.S. Food and Drug Administration BB-IND: #5370; Autologous Peripheral Blood Stem Cells Cultured Ex-Vivo with Anti-CD3 (OKT3, Ortho) and Interleukin-2 (Chiron); Transduced (L2SN, University of Minnesota) Expressing IDS Gene; approved to initiate clinical trial (June, 1995). Active clinical trial period: – January 10, 1998.
- Method for the Detection of Mucopolysaccharide Disease (Serial No. 194,553) submitted May 13, 1988; continuation-in-part (Serial No. 07/297,051) submitted January 16, 1989; amendment, Method for the detection of mucopolysaccharide storage disease, continuation-in-part (Serial No. 07/297,051) submitted May 29, 1991; patent allowed, November, 1993; patent application (Serial No. 07/806,833) Method for the Detection of Mucopolysaccharide Storage Diseases issued on May 10, 1994 as U.S. Patent No. 5,310,646.
- Whitley CB, Gorlin RJ, Krivit W. A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome. Am J Med Genet 28(1). 1987. 233-243. PMID: 3118714.
- Aronovich EL, Pan D, Whitley CB, Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency. Am J Hum Genet. 1996 Jan;58(1):75-85. PMCID: PMC1914939.
- Whitley CB, Utz JR. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): a single dose of galsulfase further reduces urine glycosaminoglycans after hematopoietic stem cell transplantation. Mol Genet Metab 101(4). 2010. 346-348. PMID: 20800524.
- Ou L, Herzog T, Koniar BL, Gunther R, Whitley CB. High-dose enzyme replacement therapy in murine Hurler syndrome. Mol Genet Metab 111(2). 2014. 116-122. doi:10.1016/j.ymgme.2013.09.008. Epub 2013 Sep 19. PMCID: PMC4014311, PMID: 24100243.
- Ou, L., DeKelver R.C., Rohde M., Tom S., Radeke R., St. Martin S., Santiago,Y, Sproul S., Przybilla M.J., Koniar B.L., Podetz-Pedersen K.M., Laoharawee K., Cooksley R.D., Meyer K.E., Holmes M.C., McIvor R.S., Wechsler T., Whitley C.B. ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome, Molecular Therapy (2018), doi: https://doi.org/10.1016/j.ymthe.2018.10.018.
- K. Laoharawee, R. DeKelver, K. Podetz-Pedersen, M. Rohde, S. Sproul, H. Nguyen, T. Nguyen, S.S. Martin, L. Ou, S. Tom, C.B. Whitley, R.S. McIvor. Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-mediated In Vivo Genome Editing. Molecular Therapy 26(4):1127-1136, April 2018. doi.org/10.1016/j.ymthe.2018.03.002
- Whitley, CB, J.M. Opitz, J.F. Reynolds. First International Congress on Mucopolysaccharidosis and Related Diseases ‐ 70 Years of Research, University of Minnesota, Minneapolis, May 20–23, 1988. Am J Med Genet 32(2) 1989. doi.org/10.1002/ajmg.1320320233
WORLDSymposium™ YOUNG INVESTIGATOR AWARDS FOR BASIC SCIENCE
Congratulations to the ten individuals who received the WORLDSymposium Young Investigator Award for 2019. The award was a partial scholarship towards attendance at WORLDSymposium 2019. Numerous individuals submitted an application for the award, and the review process was difficult due to the excellent caliber of all the applicants. WORLDSymposium would like to congratulate all of the applicants for their hard work. The following individuals received the WORLDSymposium Young Investigator Award for 2019 and were recognized at the Award Ceremony and Opening Reception on Monday, February 4 at 5:15 PM in the Regency Foyer:
- Rhea Ashmead, University of Victoria, Victoria, Canada
- Hojun Choi, Korea Advanced Institute of Science and Technology (KAIST), Daedeok Innopolis, Daejeon, South Korea
- Chloe Christensen, University of Victoria, Victoria, Canada
- Jenny Do, National Institutes of Health (NIH), Bethesda, Maryland, USA
- Areian Eghbali, National Institutes of Health (NIH), Bethesda, Maryland, USA
- Eric Joshua Garcia, National Institutes of Health (NIH), Bethesda, Maryland, USA
- Francyne Kubaski, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Murtaza Nagree, University of Toronto, Toronto, Canada
- Yanyan Peng, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
- Hiroyuki Yamakawa, Keio University School of Medicine, Tokyo, Japan