Download or read book Stem Cell Therapy in Lysosomal Storage Diseases written by Jaap Jan Boelens and published by Springer Science & Business Media. This book was released on 2013-10-10 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stem Cell therapy for lysosomal diseases (LSDs) is developing rapidly. This volume discusses the history, current practice and future perspectives of stem cells in inborn errors of metabolism (IEM) and provides an international perspective on progress, limitations, and future directions (e.g. gene therapy, iPS, ES) in the field. Beginning with an overview of these diseases, the book covers the breadth of this topic from treatment options, bone marrow transplantation, and alternative treatment options, through long-term outcomes and future perspectives.
Download or read book Introduction to Biological and Small Molecule Drug Research and Development written by Charles W. Richard and published by Elsevier Inc. Chapters. This book was released on 2013-05-07 with total page 25 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lysosomal storage disorders (LSDs) represent a group of about 50 genetic disorders caused by deficiencies of lysosomal proteins. The missing lysosomal protein causes a build-up of toxic metabolites in the cells of patients, leading to progressive multisystem disease and premature death. Although individually rare, the combined prevalence of all lysosomal disorders is estimated to be 1 in 8000 births. This chapter describes progress in several different LSD treatment modalities including enzyme replacement therapy, haematopoietic stem cell therapy, chaperone (enzyme stabilization) therapy, and substrate reductions therapy, and highlights new treatment directions for the future.
Download or read book Ex Vivo Gene Therapy for Lysosomal Storage Disease Using IPSC derived Neural Stem Cells written by Tagan Aaron Griffin and published by . This book was released on 2015 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Diseases affecting the central nervous system (CNS) pose a formidable obstacle to the delivery of effective therapeutics. A tight-knit collection of cells and macromolecules known as the blood-brain-barrier (BBB) prevents most substances from entering the brain. One intriguing approach to overcoming this obstacle involves transplanting neural stem cells (NSCs), the precursor cells to neurons and glia in the brain, as vehicles for the delivery of therapeutic proteins in their native environment. Notably, this strategy has already been successfully applied to several lysosomal storage diseases caused by genetic deficiencies in one of the many lysosomal hydrolases expressed throughout the body. A major drawback to this approach is that foreign NSCs, e.g. immortalized cell lines and primary fetal NSCs can be tumorigenic and immunogenic. Recently developed induced pluripotent stem cell (iPSC) technologies, combined with pluripotent stem cell differentiation techniques, have the potential to overcome these obstacles. This approach was evaluated using a comprehensive strategy targeting a prototypical lysosomal storage disease, Sly disease (MPS VII). MPS VII patient fibroblasts were transduced with retroviral vectors expressing the transcription factors Oct4, Sox2, Klf4, and c-Myc. Patient fibroblasts were reprogrammed into embryonic stem cell-like iPSCs that demonstrated hallmarks of pluripotency. Patient iPSCs, alongside iPSCs derived from an unaffected individual, were subjected to a stepwise differentiation protocol, yielding a relatively homogenous population of NSCs. Following in vitro characterization, patient iPSCs were genetically corrected using a DNA transposon-based vector. Transplantation of NSCs into neonatal MPS VII mice revealed that these cells could migrate long distances and survive for several months. However, corrected grafts expressing physiological levels of the missing enzyme, ?-glucuronidase, were too sparse to significantly ameliorate pathology. In contrast, the same cells transplanted into the post-symptomatic adult MPS VII striatum were restricted to the injection site. Corrected, but not uncorrected patient iPSC-NSCs, were able to restore pathologically activated microglia to a normal quiescent state in a zone surrounding the graft. Together, these results provide evidence that ex vivo NSC gene therapy may be a viable option for many lysosomal storage diseases using easily attainable, non-neural patient tissue.
Download or read book Lysosomal Storage Diseases written by Rossella Parini and published by John Libbey Eurotext. This book was released on 2010 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt: The last fifteen years have witnessed the extraordinary evolution of basic and clinical research in the field of lysoso-mal storage diseases (LSDs), transforming many of them from dire, untreatable progressive diseases to conditions that allow for possible cure or mitigation. In addition to the presently employed techniques of haematopoietic stem cell transplantation and enzyme replacement for a number of lysoso-mal storage diseases, other therapeutic approaches are being developed that are based on different principles. The awareness that the efficacy of treatment is greater if adminis-tered at the first signs of disease or, even better, during the pre-symptomatic phase underscores the urgency of early clinical diagnosis. Efforts are being made to improve the clinical acumen of paediatricians, paediatric surgeons and neurologists, rheumatologists, orthopaedists, and other professionals who come into early contact with children with LSDs. The possibility of including some of these disorders in routine neonatal screening is also a matter of discussion. This volume provides an updated overview of epidemiologic, biochemical, genetic, pathogenetic, and clinical aspects of these disorders and outlines the various treatment options currently available for the LSDs. The need for patients with rare diseases like LSDs to be followed-up in a specialised centre is emphasised in view of the many kinds of multidisciplinary treatment that are needed to improve the quality of life and survival of these children.
Download or read book Immune Responses in Patients with Lysosomal Storage Disorders Treated with Enzyme Replacement Therapy and Haemopoietic Stem Cell Transplantation written by Muhammad A. Saif and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Pediatric Neurology Part III written by Vassili Valayannopoulos and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 22 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lysosomal storage diseases (LSD) are inborn errors of metabolism secondary to lysosomal enzyme defects and are characterized by a progressive accumulation of nondigested macromolecules provoking cellular dysfunction and clinical manifestations. The diagnosis of these diseases can be confirmed easily in most cases by immuno-enzymatic techniques and molecular biology. Even though these enzymatic deficits result in an accumulation of pathological substrates, the underlying mechanisms responsible for the pathogenesis of the disease are not entirely known. Nevertheless, the distribution of the accumulated material determines the affected organs. More particularly in the central nervous system (CNS), neurons are often involved due to the accumulation of storage material and their incapacity of renewal. LSD can be responsible for mental retardation or for a neurodegenerative course in the central nervous system. The peripheral nervous system and the muscle can also be severely impaired. Hematopoietic stem cell transplantation was the first therapy, demonstrating efficacy especially on the neurological involvement of various LSD. Enzyme replacement therapy is now available for Gaucher disease, Fabry disease, mucopolysaccharidoses type I, type II, and type VI, and Pompe disease. Inhibition of the synthesis of the accumulated substrate by small molecules which also have the capacity to diffuse through the blood–brain barrier is another treatment option. New therapeutic strategies using the properties of molecular chaperones and of read-through molecules for nonsense mutations have been studied in vitro and hopefully will soon find clinical applications while intrathecal enzymes are currently studies in clinical trials for MPSII, MPS IIIA and MLD.
Download or read book Enzyme Replacement Therapies for Lysosomal Storage Diseases written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book FRONTIERS IN LYSOSOMAL STORAGE DISEASES LSD TREATMENTS written by LUNAWATI. BENNETT and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Stem Cell Therapy written by Erik V. Greer and published by Nova Publishers. This book was released on 2006 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: Among the many applications of stem cell research are nervous system diseases, diabetes, heart disease, auto-immune diseases as well as Parkinson's disease, end-stage kidney disease, liver failure, cancer, spinal cord injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Stem cells are self-renewing, unspecialised cells that can give rise to multiple types all of specialised cells of the body. Stem cell research also involves complex ethical and legal considerations since they involve adult, foetal tissue and embryonic sources. This new book brings together leading research from throughout the world in this frontier field.
Download or read book Lysosomal Disorders of the Brain written by Steven U. Walkley and published by . This book was released on 2004 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lysosomal storage diseases are inherited metabolic disorders characterized by severe pathology, typically involving the brain. Although individually rare, they collectively represent a significant group of diseases that primarily present in early infancy or childhood. In recent yearsconsiderable progress has been made in understanding the molecular mechanisms that lead to disordered function of the lysosomal system and to lysosomal storage. Unravelling the basis for these diseases is providing unique insight into the normal biology of cells and pointing the way to thedevelopment of therapeutic strategies for their treatment. Lysosomal Disorders of Brain details recent advances in the molecular and cellular pathologies of these diseases and in the development of effective therapies. After an overview of the biology of the endosomal-lysosomal system and the types of diseases resulting from defects in this system, thebook describes in detail the molecular mechanisms of storage, model systems and pathophysiological mechanisms, and finally, new advances toward treatment. With each chapter written by leading experts in their field, this book will be valuable for scientists and clinicians in helping them understandthe role of lysosomes in normal cells and mechanisms underlying these disorders, how they can be diagnosed, and the treatment options that are currently available.
Download or read book Lysosomal Storage Disorders written by Gregory M. Pastores and published by World Scientific. This book was released on 2010 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of lysosomal storage disorders, and provides the reader with an understanding of clinical features, associated complications, and diagnosis and management approaches. It also describes historical developments in the field and current thinking relating to pathophysiology and prospective therapeutic strategies. The book is written by an expert in the field who has been engaged in both basic and clinical research, in addition to having extensive practical experience in patient care. It is written from the perspective of someone who entered the field just as treatment was being introduced, and who has been engaged in the seminal clinical trials and the development of therapeutic guidelines. It offers a broad perspective and should appeal to both novices and experts in the field who seek a single resource that provides a comprehensive picture of relevant topics on this subject. A multi-faceted volume, the author addresses the issue of diagnosis and patient management, underlying mechanisms of disease, sources of morbidity and treatment options, covering issues of interest to both the basic scientist and the clinician. Sample Chapter(s). Foreword (34 KB). Chapter 1: Introduction (1,266 KB). Contents: Clinical Perspectives; Diagnostic Confirmation and Screening Protocols; Assessment of Disease Burden and Assignment of Disease Severity; Pathophysiology and Biomarkers; Current and Emerging Therapies; Future Prospects. Readership: Graduate medical students, nurses, genetic counselors and physicians.
Download or read book Stem Cell Therapy for Autoimmune Disease written by Richard K. Burt and published by CRC Press. This book was released on 2019-11-11 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stem cell transplantation may be complicated by treatment-related mortality and like the immune system that it regenerates has equal potential to either create and preserve or destroy. The dual nature that defines stem cells is differentiation that ultimately leads to death and self-renewal, which leads to immortality. What types of stem cells are there? How are they collected? What are their attributes and characteristics? This textbook devotes many chapters to familiarize the reader with the basic science, clinical aspects, and new questions being raised in the field of stem cell biology. Blood stem cells for tolerance and tissue regeneration are a rapidly developing research and clinical field that is being applied to autoimmune diseases. In clinical trials, autologous hematopoietic (blood) stem cells are being used to reduce the cytopenic interval following intense immune suppressive transplant regimens. While as yet not delineated, some possible mechanisms and pathways leading to tolerance after hematopoietic stem cell transplantation are suggested in these chapters. Tissue regeneration from blood stem cells is also suggested by animal experiments on stem cell plasticity or metamoirosis (i.e., change in fate) as described within this textbook. Ongoing early clinical trials on tissue regeneration from blood stem cells are described in the chapter on stem cell therapy for cardiac and peripheral vascular disease. Whether autologous hematopoietic stem cells, through the process of mobilization and reinfusion, may be manipulated to contribute to tissue repair in autoimmune diseases is a future area for translational research.
Download or read book Development of a Stem Cell Gene Therapy for Sanfilippo Syndrome Type B written by Don Lucas Clarke and published by . This book was released on 2017 with total page 36 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sanfilippo syndrome type B (Mucopolysaccharidosis type IIIB; MPS IIIB) is a lysosomal storage disorder affecting primarily the brain and is characterized by profound intellectual disability, dementia, and a lifespan of about twenty years. The cause is a mutation in the gene encoding alpha-- N-acetylglucosaminidase (NAGLU), a lysosomal enzyme, leading to the deficiency of NAGLU and accumulation of heparan sulfate. I am investigating a stem cell gene therapy approach in a Naglu-/- mouse model. I think that iNSCs overexpressing NAGLU can engraft and reduce neural pathology in the mouse model. Here I report that NAGLU overexpressed in neural stem cells derived from induced pluripotent stem cells (iNSCs) is capable of being taken up by deficient cells. I used flow cytometry and Lysotracker to demonstrate that NAGLU can reduce deficient cells' lysosomal volume in vitro, suggesting that NAGLU treatment has a biological effect. iNSCs overexpressing NAGLU were injected into the brains of 1 day old Naglu-/- mice. iNSCs were detected 10 weeks after injection. Brain sections possessed NAGLU activity greater than or equal to heterozygous controls, activity was detected distal to injection sites, and transplanted animals showed reduction in LAMP1, GFAP, and CD68. The results suggest that engineered iNSCs could be used to deliver enzyme and treat MPS IIIB.
Download or read book Mesenchymal Stem Cell Therapy written by Lucas G. Chase and published by Springer Science & Business Media. This book was released on 2012-12-12 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.
Download or read book Lysosomal Storage Disorders written by John A. Barranger and published by Springer Science & Business Media. This book was released on 2007-10-16 with total page 563 pages. Available in PDF, EPUB and Kindle. Book excerpt: The knowledge of lysosomal biology and the consequences of its dysfunction have increased dramatically in the past 60 years. This book describes the nature of the lysosomal dysfunction and diseases as well as potential future treatments and therapies. Disease specific chapters provide thorough reviews of the clinical features of lysosomal storage disorders, their molecular basis and the commercial or experimental therapeutic approaches sought in this area. This is an invaluable resource for researchers in biochemical and molecular genetics, enzyme therapy, and gene transfer.
Download or read book Preclinical Studies Towards Stem Cell Gene Therapy for Gaucher Diseasse written by Menzo Jans Emco Havenga and published by . This book was released on 1999 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Stem Cell Repair and Regeneration written by Nagy A. Habib and published by Imperial College Press. This book was released on 2005 with total page 305 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second book in the Stem Cell Repair and Regeneration series provides a deeper exploration of the therapeutic potential of undifferentiated human stem cells.Regenerative medicine is an extremely fast-moving field which is evolving from the initial days of hype and excitement to a more realistic appraisal of the role of stem cells in the treatment of degenerative disorders. The series aims to keep abreast of these changes by combining new knowledge in stem cell biology and therapeutic applications.The current volume contains papers by the field's leading scientists and explores the current knowledge on cell therapy for different diseases and injured organs, including diabetes, liver and heart disease.
