Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter's Hope Leukodystrophy Care Network

The leukodystrophies are a heterogeneous group of inherited disorders that disrupt myelination in the central nervous system (CNS) and may also involve the peripheral nervous system. The onset and severity of symptoms differ between diseases and may correlate with genetic mutation(s). In the most severe forms, affected individuals experience rapid, progressive, and ultimately fatal neurologic symptoms. Without newborn screening (NBS) or a known family history, the diagnosis of the index case in a family is usually delayed until symptoms are present and progress to a stage where treatment with transplantation is no longer potentially beneficial.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research

Related Links:

In this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD (mean follow-up 6.75 years, range 3 –13.5) and compared with 35 non-transplanted children with juvenile MLD. Motor function (GMFM-88 and GMFC-MLD), cognitive function (FSIQ), peripheral neuropathy (tibial nerve conduction velocity), and cerebral changes (MLD-MR severity score) were tested prospectively.Seven children remained neurologically stable over a long period, five exhibited rapid disease progression over the first 12 to 18 months after transplantation. In the latte...
Source: Molecular and Cellular Pediatrics - Category: Cytology Source Type: research
Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the natural...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: February 2020Source: Molecular Genetics and Metabolism, Volume 129, Issue 2Author(s): Isabel C. Yoon, Nicholas A. Bascou, Michele D. Poe, Maria L. Escolar
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research
We report here a successful umbilical cord blood stem cell transplantation (UCBT) for PMD in a 2-year-old boy.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 325 Source Type: research
Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Abstract Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality. Previous work showed involvement of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways, but poor PLP1 genotype-phenotype associations suggest additional pathogenetic mechanisms. Using induced pluripotent stem cell (iPSC) and gene-correction, we show that patient-derived oligodendrocytes can develop to the pre-myelinating stage, but subsequently undergo cell death. Mut...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Nalin Gupta, Roland G. Henry, Sang-Mo Kang, Jonathan Strober, Daniel A. Lim, Tamara Ryan, Rachel Perry, Jody Farrell, Mary Ulman, Raja Rajalingam, Allyson Gage, Stephen L. Huhn, A. James Barkovich, David H. RowitchSummaryFour boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells (HuCNS-SC). Subsequently, all subjects were followed for an additional 4 years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonanc...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
CONCLUSIONS: Although the complication rate for patients with Krabbe disease and metachromatic leukodystrophy is higher than the general population, most complications were mild and self-limiting. These results suggest that, in experienced hands, general anesthesia is well tolerated in most children. Findings show that the Neurodevelopment in Rare Disorders classification system is a better indicator for assessing complication risk in patients with Krabbe and metachromatic leukodystrophy than American Society of Anesthesiologists Physical Status. PMID: 31359511 [PubMed - as supplied by publisher]
Source: Paediatric Anaesthesia - Category: Anesthesiology Authors: Tags: Paediatr Anaesth Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 21 February 2019Source: Stem Cell ReportsAuthor(s): Stephanie Dooves, Prisca S. Leferink, Sander Krabbenborg, Nicole Breeuwsma, Saskia Bots, Anne E.J. Hillen, Gerbren Jacobs, Marjo S. van der Knaap, Vivi M. HeineSummaryStem cell therapy has great prospects for brain white matter disorders, including the genetically determined disorders called leukodystrophies. We focus on the devastating leukodystrophy vanishing white matter (VWM). Patients with VWM show severe disability and early death, and treatment options are lacking. Previous studies showed successful cell replacement therapy in rod...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
More News: Biology | Brain | Genetics | Hematology | Leukodystrophies | Neurology | Stem Cell Therapy | Stem Cells | Transplants