Allogenic bone marrow transplantation for late‐infantile neuronal ceroid lipofuscinosis

Yuza, Yuki; Yokoi, Kentaro; Sakurai, Ken; Ariga, Masamichi; Yanagisawa, Takaaki; Ohashi, Toya; Hoshi, Yasutaka; Eto, Yoshikatsu

doi:10.1111/j.1442-200x.2005.02126.x

Cited by 15 publications

(7 citation statements)

References 10 publications

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“…In LINCL, the only completed drug treatment study has been the melatonin study mentioned above. There have been a number of LINCL disease modification studies, such as bone marrow transplantation [ 27 – 29 ] and antioxidants (selenium, VitE, [ 30 ]). It should be noted that these antioxidant studies were completed prior to the availability of NCL molecular diagnostics.…”

Section: Pipeline For Drug Developmentmentioning

confidence: 99%

“…Some LSDs, including Hurler Syndrome, have shown potential for being treated with adipose and hematopoietic stem cells (HSC; [ 75 – 79 ]). A number of NCL mouse model and patient studies have explored the benefits of HSC therapy but met with limited success partially owing to the limited patient sample size [ 26 , 28 , 29 ]. The most promising of these studies has suggested that HSC, specifically bone marrow treatment, offered in combination with gene therapy in Ppt1 −/− mice significantly improved outcomes even when HSC therapy alone provided limited or no benefit.…”

Section: Stem Cell Therapymentioning

confidence: 99%

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Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

Geraets

Koh

Hastings

et al. 2016

Orphanet J Rare Dis

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The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, progressive neuronal degeneration and massive glial activation. Advances have been made in genetic diagnosis and counseling for families. However, comprehensive treatment programs that delay or halt disease progression have been elusive. Current disease management is primarily targeted at controlling the symptoms rather than “curing” the disease. Recognizing the growing need for transparency and synergistic efforts to move the field forward, this review will provide an overview of the therapeutic approaches currently being pursued in preclinical and clinical trials to treat different forms of NCL as well as provide insight to novel therapeutic approaches in development for the NCLs.

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Section: Pipeline For Drug Developmentmentioning

confidence: 99%

Section: Stem Cell Therapymentioning

confidence: 99%

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

Geraets

Koh

Hastings

et al. 2016

Orphanet J Rare Dis

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“…Stem cell transplantation is also considered to treat NCLs. However, hematopoietic stem cell transplantation did not perform ideally, only transient effect was observed in a few experiments (Lonnqvist et al, 2001; Yuza et al, 2005). Transplantation of neural stem cell performed better in murine model (Tamaki et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis

et al. 2019

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Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.

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“…HSC and/or UCB transplantation is the standard care for about fifteen IEM and more than 2000 treatments are reported for Asparylgrucosaminuria, Metachromatic Leucodystrophy, Fucosidosis, Adrenoleucodystrophy, Mucopolisaccharidosis type I (severe phenotype), Mucopolisaccharidosis type IV (if ERT failed), Wolman Disease, Mucolipidosis II or I-Cell Disease, Globoid Leucodystrophy [102]. For other fifteen IEM, including NCLs, HSC and UCB transplantation are in investigational phase [152][153][154], and for two it is not indicated.…”

Section: Stem Cell Therapymentioning

confidence: 99%

“…The therapeutic value of stem cell transplants was not apparent in clinical studies performed in CLN1, CLN2 and CLN3 disease patients, and even not in an animal model [55,[152][153][154]156], and it is a contra-indication of ERTs [157][158][159]. Emerging stem cell sources, such as UCB, as well as improvement of transplantation techniques, and the mechanistic fact that the macrophages of the blood surpass the BBB and integrate as microglia in the brain, may extend the list of IEM with HSCT and/or UCB indication [157].…”

Section: Stem Cell Therapymentioning

confidence: 99%

Therapeutic Approaches to the Challenge of Neuronal Ceroid Lipofuscinoses

Kohan¹,

Cismondi²,

Oller-Ramírez³

et al. 2011

CPB

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The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally with recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 269 mutations and 49 polymorphisms (http://www.ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.

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Allogenic bone marrow transplantation for late‐infantile neuronal ceroid lipofuscinosis

Cited by 15 publications

References 10 publications

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis

Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis

Therapeutic Approaches to the Challenge of Neuronal Ceroid Lipofuscinoses

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