Benefits of Newborn Screening and Hematopoietic Cell Transplant in Infantile Krabbe Disease.
Date
2022-01-18
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
Infantile Krabbe Disease (IKD) can be treated with hematopoietic cell transplantation (HCT) if done during the first weeks of life before symptoms develop. To facilitate this, newborn screening (NBS) has been instituted in eight U.S. states. An application to add KD to the Recommended NBS Panel (RUSP) is currently under review. In this report, the outcomes of newborns with IKD diagnosed through NBS and treated with HCT are presented. The unique challenges associated with NBS for this disease are discussed including opportunities for earlier diagnosis and streamlining treatment referrals. This is a retrospective review of infants with IKD detected by NBS and referred for HCT. The timing from diagnosis to HCT were examined and both HCT and neurodevelopmental outcomes are described. Six infants were diagnosed and referred for HCT. Neurologic testing before HCT revealed evidence of active IKD in all infants. All underwent HCT between 24-40 days of age, successfully engrafted, and are alive 30-58 months later (median, 47.5 months). All are gaining developmental milestones albeit at a slower pace than unaffected age-matched peers. Gross motor function is most notably affected. NBS for these patients enabled early access to HCT, the only currently available treatment for infants with IKD. All children are alive and have derived developmental and neurologic benefits from timely HCT. Long-term follow up is ongoing. Optimization of HCT and further development of emerging therapies, all of which must be delivered early in life, are expected to further improve outcomes of infants with IKD.
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Page, Kristin M, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, et al. (2022). Benefits of Newborn Screening and Hematopoietic Cell Transplant in Infantile Krabbe Disease. Blood advances. 10.1182/bloodadvances.2021006094 Retrieved from https://hdl.handle.net/10161/24561.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
James Michael Provenzale
I have the following major research areas:
I. Diffusion tensor imaging (an MR technique that measures rate and direction of microscopic water motion) to examine white matter pathways in the brain. This technique is used by many investigators in an attempt to understand white matter microstructure. My recent work has centered on the histological correlation of DTI metrics. In addition, because DTI metrics can vary substantially within a single scanner at multiple time points as well as between scanners, my work is focused on understanding causes of such variability and designing methods to decrease it.
Since 1998, I have mentored third-year students at Duke University School of Medicine (typically one medical student per year) in both DTI research and perfusion imaging research. Although the research techniques are highly advanced, our implementation of various "user-friendly" software programs allows students with little or no prior experience to analyze data in a productive manner. Our research is also well-suited to individuals with advanced computer skills or an interest in biomedical or electrical engineering. Students work closely with research personnel on a daily basis. They also meet with collaborators from various basic science and clinical departments and me in a laboratory meeting once a week. The focus of these meetings is to plan experiments, refine research methods, discuss experimental results and prepare manuscripts. Students serve as first authors or co-authors on manuscripts based on their specific research project. The results of a number of such projects have been published.
II. Applications of nanotechnology to treatment of cancer (both CNS and non-CNS) and brain disorders. My research involves design and implementation of nanoparticles and fluorescent molecules for cancer diagnosis and therapy. Although I am trained as a neurologist and neuroradiologist, most of my nanotechnology-based research is oriented towards non-CNS tumors such as breast cancer and sarcomas. In the past few years, my Emory and Georgia Tech colleagues and I have conducted research using animals with naturally-occurring tumors at the University of Georgia College of Veterinary Medicine. This work has focused on the use of a handheld device to detect fluorophores that are administered intravenously prior to surgery. We are presently validating the use of this combination of imaging device and contrast agent to guide surgical resection of tumors. I am also interested in development of nanotechnology-based non-invasive and minimally invasive devices that can continuously monitor tumor physiological characteristics and response to therapy. This work is done in conjunction with a number of colleagues in Biomedical Engineering at both Duke and Emory and supported by a number of NIH grants. Finally, I have a strong interest in use of nanotechnology for tissue engineering and regenerative medicine.
Kathryn E. Gustafson
My scholarly interests and expertise are in pediatric neurodevelopmental outcomes assessment and research as well as child and parent coping with chronic childhood illness. In the 1990s, I collaborated with Dr. Robert Thompson in investigating the transactional biopsychosocial model of adaptation to pediatric conditions in children and families. Our research program was funded by the NIH and culminated in the publication of our book, Adaptation to Chronic Childhood Illness. Since that time, I have worked closely with the Division of Neonatology and the Duke Neonatal-Perinatal Research Unit on neurodevelopmental outcomes research with high-risk infants, toddlers, and school-age children. I am a gold standard psychology consultant to the Neonatal Research Network (NRN) of the NIH/NICHD, train and certify psychologists nationally and internationally in infant and toddler developmental assessment for numerous research groups, and serve as consultant for protocol development. In addition, I collaborate with colleagues in Pediatric Ophthalmology to investigate preterm optic nerve anatomy assessed via optical coherence tomography imaging and the association with neurodevelopment. I am also involved in investigations of umbilical cord blood stem cell transplant for young children with hypoxic ischemic encephalopathy, cerebral palsy, and inborn errors of metabolism, such as Krabbe disease, with colleagues in the Pediatric Transplant and Cellular Therapy program.
Joanne Kurtzberg
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University. The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program. The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.
Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.
In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA. She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.