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SPARKLE is an alpha-mannosidosis registry that aims to gather long-term safety and effectiveness data on the use of velmanase alfa in routine clinical care in patients with alpha-mannosidosis. It is a post-approving pledge to European marketing approval for Velmanase alfa, the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. The primary success measure is a global treatment response rate, determined as the individual sum of single endpoints from pharmacodynamic, physiological, and quality of life health outcomes; secondary effectiveness studies are used to describe the patient population with alpha-mannosidosis with respect to clinical manifestation, progression, and natural history of the disease. Conclusion: This report will include real-world evidence on velmanase alfa's long-term safety and effectiveness in patients with alpha-mannosidosis during routine clinical care and improve patient recognition of the disease's path, clinical manifestations, and progression of this ultra-rare disease.
Source link: https://doi.org/10.21203/rs.2.19376/v2
Velmanase alfa, a human recombinant alpha-mannosidase, was approved in Europe in 2018 as the first enzyme replacement therapy for the treatment of non-neurologic abnormalities in patients with mild-to-moderate alpha-mannosidosis. SPARKLE, an alpha-mannosidosis registry study that aims to obtain long-term safety and effectiveness data on the use of velmanase alfa in routine clinical care in patients with alpha-mannosidosis patients with alpha-mannosidosis patients with alpha-mannosidosis, as well as a post-approval pledge to European market approval. The primary effect of effectiveness is a global treatment response rate, assessed as the individual sum of single endpoints from pharmacodynamic, functional, and quality of life improvement results; secondary effectiveness findings are used to map the patient population of patients with alpha-mannosidosis with respect to clinical appearance, expansion, and natural history of the disease.
Source link: https://doi.org/10.21203/rs.2.19376/v1
Abstract Introduction: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder characterized by reduced alpha-mannosidase synthesis. This research was designed to investigate the age of death and causes of death among patients with alpha-mannosidosis who did not receive disease-modifying therapy. Methods Clinicians and LSD patient organisations from 33 countries were encouraged to complete a questionnaire between April and May 2021. Median age at death for patients reported by physicians/POs was 45 years old, with 53% being female. One death occurred during the patient's second decade of life, and 14 out of 15 deaths during or after the patients' third decade, with four of them during their sixth decade. Patients identified from the literature's death was 4. 3 years old, two of whom were female, and two were male. Conclusions This report shows that pneumonia has been the leading cause of death in untreated patients with alpha-mannosidosis for the past decade, followed by cancer.
Source link: https://doi.org/10.1186/s13023-022-02422-6
Dendrites at the axon hillock are present in a variety of neuronal storage diseases, cortical pyramidal cells, and cortical pyramidal cells. An elevated level of GM2 ganglioside in cerebral cortex is a characteristic of all the diseases characterized by ectopic dendrites. The number of pyramidal cells bearing ectopic dendrites in cats with one of these disorders, alpha-mannosidosis, is small in cats with one such disease, alpha-mannosidosis; the current research shows that GM2 ganglioside is only present in pyramidal neurons with ectopic dendrites. The application of a monoclonal antibody against GM2 ganglioside showed that subsets of both pyramidal and intrinsic neurons had GM2-like immunoreactivity. Every GM2+ cell contained PAS+ membranous inclusions, indicating that pyramidal cells carrying ectopic dendrites stored GM2 ganglioside. Some pyramidal neurons produced GM2-like immunoreactivity after 4 weeks of therapy, whereas ectopic dendrites were only apparent after 7 weeks of treatment.
Source link: https://doi.org/10.1073/pnas.88.24.11330
Human alpha-mannosidase activity from tissues and cultured skin fibroblasts was separated by gel electrophoresis into a neutral, cytoplasmic form, as well as two closely related acidic, lysosomal components. In human-mouse and human-Chinese somatic cell hybrids, the gene coding for human alpha-mannosidase B has been determined. The human alpha-mannosidase B phenotype showed congregation with the human enzyme glucosephosphate isomerase, but not in the case of 30 other enzyme markers identifying 20 linkage groups. The alpha-mannosidase B structural gene was assigned to chromosome 19 in man by this MANB-GPI linkage and reporting chromosome findings.
Source link: https://doi.org/10.1073/pnas.74.7.2968
Alpha-Mannosidosis is an extremely rare storage disorder caused by a deficiency of lysosomal alpha-mannosidase encoded by the MAN2B1 gene. AM's research here presents the medical and genetic analysis of six patients from two Tunisian families. ES tests revealed a missense mutation p. in the MAN2B1 gene in four affected family members for the second family. The p. mutation results in a premature termination codon that may lead to DNA degradation by the NMD device. The reduction of the MAN2B1 synthesis's synthesis may explain the index case's severe phenotype. According to the literature, the p. missense variant has no effect on MAN2B1 maturation and transportation, which is related to a moderate clinical subtype. To illustrate the intra-familial variability of cognitive impairment, exome analysis revealed two potential pathogenic variants in GHR and SLC19A3 genes that could be attributed to cognitive decline.
Source link: https://doi.org/10.1371/journal.pone.0258202
SPARKLE is an alpha-mannosidosis registry that aims to collect long-term safety and effectiveness data on the use of velmanase alfa in routine clinical care in patients with alpha-mannosidosis. The SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis that will begin in 2020. The most important success result is a global treatment response rate, determined as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life clinical studies; secondary effectiveness studies are used to identify the patient population with alpha-mannosidosis with respect to clinical manifestation, change, and natural history of the disease. The aim of this research will provide real-world evidence on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and help raise the level of this extremely rare disease's natural course, clinical signs, and progression of this ultra-rare disease.
Source link: https://doi.org/10.1186/s13023-020-01549-8
Alpha-mannosidosis, a rare lysosomal storage disorder with a heterogeneous clinical appearance, is a rare lysosomal storage disorder with a heterogeneous clinical appearance. The older child had a pronounced phenotype with multisystem involvement, and had progressive decline in her motor and cognitive function as a result of progressive decline. The second child has a less frequent disease course. During the disease course, therapeutic options for this disorder are limited to bone marrow transplant early in the disease course.
Source link: https://doi.org/10.1177/0883073812470973
On the lectin's chemical analysis, peripheral cell and pancreatic agglutinin cells, Tese agglutinin, Lens tyl-agglutinin, Racinus agglutinin, Arachis hypoglutinin, agglutinin, Tyrricum vulgaris agglutinin, N-acetyl-glucose, agglutinin, Tyretyl-a a agglutinininininininininininininininininininininininininininininininin Swainsonine, calystegine B 1, calystegine B 2, calystegine B 2, calystegine B 2, calystegine B 2, calystegine B 2, calystegine B 2, calystegine B 2, and calystegine C 1 were identified by the chemical analysis of dried leaves of I. verbascoidea, Calystegine C 1 t In goats, I. verbascoidea causes u03b1-mannosidosis.
Source link: https://doi.org/10.1177/1040638711425948
Gene expression in large animals' brains has been more limited in comparison to rodents, making this therapy more appropriate for treating the global brain lesions present in most human neurogenetic disorders. A hu. 32 vector expressing the green fluorescent protein reporter gene was tested in the cat to determine the possibility for therapeutic use of the hu. 32 serotype in a gyrencephalic brain of larger mammals. In the cat homologue of the human lysosomal storage disease alpha-mannosidosis, which has globally distributed lysosomal storage lesions in the brain, the therapeutic potential of a hu. 32 serotype vector was tested. Treated alpha-mannosidosis cats had reduced incidence of neurological abnormalities and longer life spans when compared to untreated cats. Systemic adeno-associated virus delivery in human neurological disorders with widespread brain lesions would appear to be a significant advantage for efficient treatment of the gyrencephalic brain.
Source link: https://doi.org/10.1093/brain/awaa161
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