China
Africa
Explore chapters and articles related to this topic
Immunological Aspects of Multiple Sclerosis with Emphasis on the Potential Use of Autologous Hemopoietic Stem Cell Transplantation
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Paolo A. Muraro, Henry F. McFarland, Roland Martin
A potential for promotion of CNS repair by HSCT can be at present only hypothesized on the basis of elegant experiments in animal models. The potential migration of hemopoietic stem cells in the CNS has been shown by work by Wu et al, who used green fluorescent protein (GFP)-transfected bone marrow graft to investigate the distribution of hematogenous cells after bone marrow transplantation in the twitcher mice.70 The twitcher mouse, bearing a mutation in the galactosylceramidase gene (twi-/twi-) is a murine model of a human genetic demyelinating disease, globoid cell leukodystrophy (Krabbe’s disease). The affected mice usually die before reaching age 45 days, showing apoptotic death of oligodendrocytes and demyelination associated with extensive glial activation. Following bone marrow transplant, many GFP positive cells were detected in the white matter of the spinal cord, brainstem and brain, demonstrating the migration of progenitor cells to CNS sites. Furthermore, work by Mezey and colleagues showed that bone marrow cells from adult mice can migrate into the brain and originate cells that express neural-specific antigens, strongly supporting the potential for transdifferentiation of hemopoietic stem cells into neural lineages.71 Whether, and to which extent, these processes may take place and play a significant role in humans with MS are exciting questions that still need to be addressed.
A new compound heterozygous mutation in adult-onset Krabbe disease
Published in International Journal of Neuroscience, 2020
Xianghe Meng, Yingjiao Li, Yajun Lian, Yujuan Li, Liyuan Du, Nanchang Xie, Cui Wang
To date, all reported cases of KD have been attributed to mutations in the galactosylceramidase gene (GALC), which encodes a galactosyl-sphingolipids (galactosylceramide, psychosine) degrading enzyme that is essential for myelin synthesis. Sequencing of all exons of GALC revealed a c.1901T > C（p. L634S）and c.1005C > G (p. Y335X) heterozygous mutation in our patient. The mutation c.1901T > C（p. L634S）was first reported in a Japanese patient with late-onset KD [23], and thereafter, in many late-onset patients with KD [2,24–26]. Therefore, our result supports previous conclusions that all phenotypes of this mutation are expressed in the late-onset form of KD. The mutation c.1005C > G (p. Y335X) is a new nonsense mutation which results in a truncated, non-functional protein. However, in the adult-onset KD phenotype, no clear genotype–phenotype relationship has been reported [3]. This study suggests that exome sequencing of GALC should be performed in patients exhibiting adult-onset spastic paraparesis or demyelination of parts of the white matter. Identification of these mutations and their associated phenotypes is important to predict the prognosis of KD, and to provide adequate genetic counseling to patients and families.
Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns
Published in Expert Review of Molecular Diagnostics, 2018
David Millington, Scott Norton, Raj Singh, Rama Sista, Vijay Srinivasan, Vamsee Pamula
NBS for LSDs, a group of approximately 40 IMDs that were not previously accessible to NBS, gained momentum in the early 2000s with the development of fluorometric enzymatic assays including alpha-iduronidase (IDUA), alpha-galactosidase (GLA) and acid alpha-glucosidase (GAA), the enzymes deficient in Hurler Syndrome (MPS I), Fabry Disease and Pompe Disease (GSD-II), respectively [6–8]. The development of enzyme replacement therapies for these and other LSDs generated even more interest in NBS to find patients that could most benefit from early treatment [5]. Accordingly, NBS for Pompe disease started in Taiwan, which has a relatively high incidence of this LSD compared with other ethnic groups, using an adaptation of the benchtop microfluorometric assay [34]. Results showed convincingly that NBS for LSDs was viable, and outcomes for cases of infantile Pompe disease were much better when treatment was provided soon after birth [35,36]. In the meantime, a method to screen for galactosylceramidase (GALC), the enzyme deficient in Krabbe disease, using MS/MS with a non-fluorogenic synthetic substrate, was introduced [9]. Cases of early onset Krabbe disease reportedly were treated successfully by bone marrow transplantation [37] and the family of one such case subsequently lobbied successfully to introduce NBS for Krabbe in New York State.