Once your neurologist suspects or confirms your diagnosis as Krabbe disease, it’s important to get connected to the right experts. Due to the complexity of this rare disease, it’s likely your care team has never encountered another patient with this condition. It’s imperative that your family member receives the most innovative options for treatment and management of the disease.
The following have been identified as leaders in the care and clinical management of Krabbe disease. As a rare disease organization, we are grateful for each of the below experts whom are well known around the world for their program and can meet the extensive medical needs of patients with Krabbe disease.
Ernesto Bongarzone, Ph.D.
Dr. Ernesto R. Bongarzone holds a doctorate in neuroscience from the University of Buenos Aires, Argentina. Currently, Dr. Bongarzone is a tenured full professor in neuroscience at the College of Medicine at the University of Illinois, Chicago (UIC). After finishing a postdoctoral training on oligodendrocyte biology at the Developmental Biology Group at the Neuropsychiatric Institute at UCLA, Dr Bongarzone took on a leadership position at the Telethon Institute for Gene Therapy in Milan, Italy. During this stage, his laboratory focused on gene and cell therapy for inherited leukodystrophies, particularly on Krabbe’s disease. In 2006 Dr Bongarzone was recruited as a faculty in the Department of Anatomy and Cell Biology at UIC and initiated a larger program on gene therapy for Krabbe’s disease, with a special interest on mechanisms of neuropathology. In parallel, his laboratory also studies mechanisms of myelin remodelling in the adult brain, pathogenesis of multiple sclerosis and the role of lysosomal dysfunction in adult onset neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, dementia and chronic traumatic encephalopathy.
Allison Bradbury, Ph.D.
Allison Bradbury is a NRSA Postdoctoral Research Fellow in the lab of Charles H. Vitae, DVM, Ph.D., ACVIM (Neurology) at the School of Veterinary Medicine at the University of Pennsylvania. She received her Ph.D. in Biomedical Sciences from Auburn University in 2014, focusing her doctoral research on adeno-associated virus (AAV) gene therapy in a feline model of GM2 Gangliosidosis, also known as Sandhoff disease. As a NRSA Postdoctoral Research Fellow in the lab of Dr. Vite, Allison is currently evaluating disease mechanisms and developing gene therapy approaches in the canine model of Krabbe disease. She has conducted a comprehensive natural history study in the canine model of Krabbe disease and demonstrated therapeutic efficacy in this model for the first time by utilizing AAV gene therapy to target both central and peripheral nervous systems.
Dr. Maria Escolar
Dr. Maria Escolar is a tenured Professor of Pediatrics and Neurodevelopmental Disabilities at the University of Pittsburgh. She graduated with a Master of Science in Nutrition from Columbia University and completed her esidency and fellowship at Cornell University Medical Center. Dr. Escolar began her research on rare neurodegenerative disorders in 2000, when she established the Program for the Study of Neurodevelopment in Rare Disorders (NDRD). Since then, she’s published over 70 original research papers in peer-reviewed journals, including two influential publications in the New England Journal of Medicine. Dr. Escolar is interested in the interactions of genes, brain, and behavior. She explores the use of biomarkers, as well as how neurobehavioral, neuroradiological, and neurodevelopmental outcome measures can be used to determine the extent of disease progression in patients suffering from rare diseases. More specifically, her research is focused on studying the natural course of rare genetic neurodegenerative diseases through neuroradiological testing, behavioral phenotype, genetic mutations, and the investigation of biomarkers, made possible through the NDRD’s longitudinal tissue repository. Dr. Escolar has strong interests surrounding the developmental of novel quantitative neuroimaging techniques that allow for longitudinally tracking changes in white matter throughout the disease process. In parallel, her focus on generating atlases of normal brain development allows for comparison between normal and aberrant neurological development and further contributes to the scientific community’s understanding of abnormal brain morphology. Lastly, Dr. Escolar and her team are spearheading a project investigating the use of gene therapy as a treatment for Krabbe disease. Dr. Escolar’s NDRD program is multidisciplinary and has the objective to improve the life of children and families living with rare neurodegenerative disorders. She provides clinical service to more than 1000 patients globally. Dr. Maria Escolar, along with The Legacy of Angels Foundation, established the KTRN, Krabbe Translational Research Network meeting. The KTRN is a consortium of scientists and clinicians who are dedicated to helping children with Krabbe disease live longer and healthier lives. The KTRN brings together the complementary knowledge and skills of investigators from different institutions and working in different disciplines to accelerate the development of research findings into new treatments. Dr. Escolar is passionate about training the new generation of health care providers that wish to develop careers in clinical research of rare neurodevelopmental disorders.
Dr. Laura Feltri
Dr. Feltri is Professor of Biochemistry and neurology at the Jacobs School of Medicine and Biomedical Sciences at the State University of New York at Buffalo. Dr. Feltri received her medical degree from the University of Milano, Italy. She completed her internship in Medicine and Residency in Neurology in the San Raffaele Hospital, University of Milano, Italy. She was a neuroscience post-doctoral fellow at Thomas Jefferson University and at the University of Pennsylvania. Dr. Feltri worked from 1993 to 2011 at the San Raffaele Scientific Institute of Milano, Italy, where she was the Head
of the Unit of Neuro-Glia. She was named an adjunct Associate Professor in the University at Pennsylvania School of Medicine’s neurology department in 2002 while continuing her work in Milan. Dr. Feltri’s scientific interest focus on myelin and myelin diseases. Together with the laboratory of Lawrence Wrabetz, she helped pioneered conditional transgenesis in Schwann cells to understand the role of extracellular matrix components and their receptors in developing and pathological peripheral nerves. Her laboratory has identified the diverse roles and many of the downstream signals for laminin receptors in nerve development. Together with Dr. Daesung Shin and Dr. Wrabetz, the lab is currently using several genetic approaches to reveal the mechanisms of Krabbe disease with the goal to design more effective therapies.
Steven Gray, Ph.D.
Dr. Steven Gray earned his Ph.D. in molecular biology from Vanderbilt University in 2006, after receiving a B.S. degree with honors from Auburn University. He performed a postdoctoral fellowship focusing on gene therapy in the laboratory of Jude Samulski at UNC Chapel Hill. He is currently an Associate Professor in the Department of Pediatrics at the University of Texas Southwestern Medical Center. Dr. Gray is the director of the UTSW Viral Vector Facility and maintains affiliations with the Department of Molecular Biology, the Department of Neurology and Neurotherapeutics, the Eugene McDermott Center for Human Growth and Development, and the Hamon Center for Regenerative Science and Medicine at UT Southwestern. He also maintains an adjunct faculty appointment in the Department of Pediatrics and the Carolina Institute for Developmental Disorders at the University of North Carolina at Chapel Hill.
Dr. Gray’s core expertise is in AAV gene therapy vector engineering, followed by optimizing approaches to deliver a gene to the nervous system. His major focus is in AAV vector development to develop vectors tailored to serve specific clinical and research applications involving the nervous system. These include the development of novel AAV capsids amenable to widespread CNS gene transfer. As AAV-based platform gene transfer technologies have been developed to achieve global, efficient, and in some cases cell-type specific CNS gene delivery, his research focus has also included preclinical studies to apply these reagents toward the development of treatments for neurological diseases. Currently these include preclinical studies for Rett Syndrome, Giant Axonal Neuropathy (GAN), Tay-Sachs, Sandhoff, Krabbe, AGU, Charcot-Marie Tooth, and Batten Diseases, and have expanded into human clinical studies to test a gene therapy approach for GAN.
Dr. Gray has published over 50 peer-reviewed papers in journals such as New England Journal of Medicine, Molecular Therapy, Nature Biotechnology, Gene Therapy, and The Proceedings of the National Academy of Sciences. He also has 3 pending patents. His research is funded by the National Institute for Neurological Disorders and Stroke, as well as numerous large and small research foundations. Dr. Gray was recently recognized with the 2016 Healthcare Hero award by the Triangle Business Journal, and his work on GAN was featured in a story by the CBS National Evening News in 2015.
Julia Kofler, MD
Dr. Julia Kofler holds a medical degree from the University of Vienna, Austria. After completing a residency in Anatomic Pathology and a fellowship in Neuropathology, she joined the pathology faculty at the University of Pittsburgh in 2010. In 2012, Dr Kofler became the director of the Neuropathology core of the Alzheimer’s disease research center, where she oversees the banking, diagnostic evaluation, and annotation of donated brains and spinal cords and manages the distribution of neurodegenerative brain tissue samples to interested local, national and international researchers. The brain bank at the University of Pittsburgh is in existence for over 30 years now and has collected >1600 cases, including Alzheimer’s disease and other dementias, Amyotrophic Lateral Sclerosis, Parkinson’s disease and other movement disorders, and traumatic brain injury. While the original focus of the brain bank was on adult neurodegenerative disease, in 2015 the brain bank was expanded to include pediatric leukodystrophies and storage disorders, with a special focus on Krabbe disease. In collaboration with Dr Maria Escolar at Children’s hospital of Pittsburgh, nine cases of Krabbe disease have been donated to the brain bank in a two-year period, which now represents the largest collection of Krabbe disease tissue samples in the country. Examination of these invaluable specimens will increase our understanding of the pathologic disease spectrum, possible associations with genetic mutations, underlying pathobiologic processes and impact of new treatment modalities.
Joanne Kurtzberg, MD
Dr. Joanne Kurtzberg is the Director of the Marcus Center for Cellular Cures and the Leukodystrophy Care Center at Duke University Medical Center. She established the Pediatric Blood and Marrow Transplant Program at Duke in 1990 and the Carolinas Cord Blood Bank at Duke, an FDA licensed public cord blood bank in 1998. Dr. Kurtzberg has focused a large part of her career on studying the use of umbilical cord blood and cord tissue cells in treating children with genetic and acquired brain disorders. She had transplanted approximately 400 children with lysosomal and peroxisomal storage diseases and other leukodystrophies with unrelated donor cord blood over the past 20 years. She developed a novel cell therapy product, DUOC-01, to augment a standard cord blood transplant hoping to deliver donor microglial cells to the brain accelerating engraftment of donor cells in the brain after a standard transplant. In addition, Dr. Kurtzberg is developing cord blood and cord tissue cell-based reparative therapies for children with hypoxic brain injuries, in utero stroke, cerebral palsy and autism and for adults with acute ischemic stroke. Dr. Kurtzberg is a strong advocate for children and families with these disorders and serves on several committees influencing Federal policies and legislation for children with serious and life-threatening illnesses.
Mark Sands, Ph.D.
Mark S. Sands, Ph.D. is a Professor in the Departments of Internal Medicine and Genetics at Washington University School of Medicine. Dr. Sands received a B.S in Nuclear Medicine from Rochester Institute of Technology in 1980. He then worked as a Research Technician in the Radiology Department at the University of Rochester School of Medicine from 1980 to 1984. Dr. Sands ventured on to receive a Ph.D. in Molecular Pharmacology from the State University of New York at Stony Brook in 1990 and became a postdoctoral research fellow at The Jackson Laboratory (Bar Harbor, ME), where his interest in Lysosomal Storage Diseases sprouted. He then performed a short post-doctoral fellowship at the University of Pennsylvania School of Veterinary Medicine before joining the faculty at Washington University School of Medicine in 1994. Since then Dr. Sands has run an independent research laboratory with the goals of better understanding the underlying pathogenesis and developing effective therapies for inherited childhood diseases; specifically, lysosomal storage diseases. Over the past ~30 years Dr. Sands’ research has focused on stem cell-mediated therapy, gene therapy, small molecule drugs and more recently on rational combinations of these approaches. The primary diseases that Dr. Sands studies are Krabbe disease, Mucopolysaccharidosis type VII and Infantile Neuronal Ceroid Lipofuscinosis.
David A Wenger, PhD
Dr. David Wenger began his academic career in 1971 in the Department of Pediatrics at the University of Colorado-School of Medicine after completing a post-doctoral fellowship at the Weizmann Institute in Israel with Dr. John S. O’Brien; the doctor who identified the gene causing Tay-Sachs disease. The following year, Dr. Wenger began studies on the purification of galactocerebrosidase (GALC), the enzyme missing in affected patients with Krabbe disease. Then in 1973, he received his first patient samples for diagnostic studies, instituting the Lysosomal Diseases Testing Laboratory. To date, Dr. David Wenger laboratory has diagnosed over 700 patients with Krabbe disease; His laboratory is located at the Jefferson Medical College in Philadelphia.
Dr. David Wenger’s dedication to Krabbe disease continued to strengthen as he, with others, cloned the saposin gene in 1986-a protein responsible for lysosomal degradation of many sphingolipids. Seven years later, with the help of a post-doctoral fellow Chen Yue Qun, he purified the GALC enzyme and cloned the gene. This discovery earmarked their ability to identify mutations such as the large deletion (30kb), the most common pathogenic variant in the European Krabbe population, along with 60 additional mutations.
Currently, Dr. David Wenger is working with a viral vector called AAVrh10-containing GALC cDNA with blood stem cell therapy to treat the mouse model of Krabbe disease. Intravenous injection of this vector shows great promise in delaying the onset of clinical findings, improving myelination, and delivering GALC activity to all nervous tissues, including the peripheral nervous system. Since blood stem cell transplantation in pre-symptomatic and mildly affected later-onset human patients is the current “standard of care,” the addition of a single intravenous injection of this viral vector to the treatment protocol appears to provide a large boost to the effectiveness of treatment. The viral vector will rapidly provide ample GALC activity to all critical tissues and the blood stem cells will improve the inflammatory component found in this disease. Affected mice undergoing this treatment are doing very well, some living two years versus 40 days when untreated. More studies to evaluate the timing of treatment and dosing of viral vector are underway. Studies are in progress in the dog model and rats to evaluate safety and effectiveness, with hopes of leading to a human trial soon.
Dr. Larry Wrabetz
Dr. Wrabetz is Distinguished Professor of Neurology and Biochemistry at the Jacobs School of Medicine and Biomedical Sciences at University at Buffalo. Dr. Wrabetz received his bachelor’s degree at Marquette University in Milwaukee, WI, in 1980 and his medical degree from the University at Chicago’s Pritzker School of Medicine in 1984. He completed his residency in neurology at the Hospital of the University of Pennsylvania in Philadelphia, PA, followed by a two-year Dana Foundation postdoctoral fellowship and an advanced postdoctoral fellowship, both in neuroscience, at University at Pennsylvania School of Medicine. He held a faculty appointment at Pennsylvania School of Medicine’s Department of Neurology for two years, and then joined the San Raffaele Scientific
Institute in 1993 as a researcher in the Department of Genetics and Cell Biology. Wrabetz was named to head the Institute’s Biology of Myelin unit in 1995, and in 2001 became affiliated with the Joseph Stokes, Jr., Research Institute of Children’s Hospital of Philadelphia. He was named an adjunct
Associate Professor in the University at Pennsylvania School of Medicine’s neurology department in 2002. The Wrabetz laboratory has worked for ~30 years on the formation and repair of myelin, with a special interest in genetic disorders with this root cause, including leukodystrophies such as Krabbe disease and Charcot-Marie-Tooth neuropathies. As a clinician, Dr. Wrabetz has diagnosed and
treated children with myelin specific disorders leading to better ways to translate research into
therapies. Dr. Wrabetz has generated many animal models of inherited neuropathies and discovered how endoplasmic reticulum stress contributes to some of these diseases, paving the way for the development of new therapies. His work in Buffalo is dedicated to the use of genetic animal models to understand and treat Krabbe disease and inherited neuropathies and to optimize Krabbe disease diagnosis and newborn screening.