Human Olfactory Ensheathing Cell Transplantation Improves Motor Function in a Mouse Model of Type 3 Spinocerebellar Ataxia

Hsieh, Jeanne; Liu, Jen Wei; Harn, Horng Jyh; Hsueh, Kuo Wei; Rajamani, Karthyayani; Deng, Yu Chen; Chia, Chih Min; Shyu, Woei Cheang; Lin, Shinn Zong; Chiou, Tzyy Wen

doi:10.1177/0963689717732578

Cited by 13 publications

(7 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An alternative strategy for 5-HT modulation is cell therapy. Intracranial human olfactory ensheathing cell transplantation prevented PC loss and enhanced motor coordination through increased expression of TPH2 [118].…”

Section: Serotonergic Systemmentioning

confidence: 98%

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies

Chen

Hong

Lin

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes. The three major conclusions from the current studies are summarized as follows: (i) for the drugs currently being tested in clinical trials; a weak connection was observed between drugs and SCA3/MJD biomarkers. The only two exceptions are the drugs suppressing glutamate-induced calcium influx and chemical chaperon. (ii) For most of the drugs that have been tested in animal studies, there is a direct association with pathological biomarkers. We further found that many drugs are associated with inducing autophagy, which is supported by the evidence of deficient autophagy biomarkers in SCA3/MJD, and that there may be more promising therapeutics. (iii) Some reported biomarkers lack relatively targeted drugs. Low glucose utilization, altered amino acid metabolism, and deficient insulin signaling are all implicated in SCA3/MJD, but there have been few studies on treatment strategies targeting these abnormalities. Therapeutic strategies targeting multiple pathological SCA3/MJD biomarkers may effectively block disease progression and preserve neurological function.

show abstract

Section: Serotonergic Systemmentioning

confidence: 98%

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies

Chen

Hong

Lin

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Olfactory dysfunction is one of the main non-motor symptoms that was already described in patients with MJD [23,24]. In a previous study, transplantation of olfactory ensheathing cells, which are specialized glial cells of the primary olfactory system, were found to improve motor function in an MJD mice model, and were suggested as a novel potential strategy for MJD treatment [25]. Vesicle transport and synaptic pathways were also implicated in MJD, as well as in other neurodegenerative diseases [26,27].…”

Section: Aging Discussionmentioning

confidence: 97%

Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Akçimen

Martins

Liao

et al. 2020

Aging

View full text Add to dashboard Cite

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson's correlation coefficient R 2 = 0.62). Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10 −5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.

show abstract

“…Olfactory dysfunction is one of the main non-motor symptoms that was already described in patients with MJD [36,37]. In a previous study, transplantation of olfactory ensheathing cells, which are specialized glial cells of the primary olfactory system, were found to improve motor function in an MJD mice model, and were suggested as a novel potential strategy for MJD treatment [38]. Vesicle transport and synaptic pathways were also implicated in MJD, as well as in other neurodegenerative diseases [39,40].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Akçimen

Martins

Liao

et al. 2019

Preprint

View full text Add to dashboard Cite

34Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia 35 worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies 36 have revealed that the length of the expansion partly explains the disease age at onset (AO) 37 variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five 38 different geographical origins, a genome-wide association study (GWAS) was conducted to 39 identify additional AO modifying factors that could explain some of the residual AO variability. 40 We identified nine suggestively associated loci (P < 1 × 10 −5 ). These loci were enriched for genes 41 involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, 42 associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms 43 might be implicated in MJD pathogenesis. Our study demonstrates the existence of several 44 additional genetic factors, along with CAG expansion, that may lead to a better understanding of 45 the genotype-phenotype correlation in MJD. 46 Keywords 47 65 collaborative studies are required to identify genetic modifiers in MJD, as well as replicate the 66 findings of such studies [8]. 67 Previously, Genetic Modifiers of Huntington's Disease (GeM-HD) Consortium carried out a GWA 68 approach of HD individuals to reveal genetic modifiers of AO in HD [9,10]. A total of eleven [9]69 and fourteen loci [10] were found to be associated with residual age at HD onset. In the present 70

show abstract

Human Olfactory Ensheathing Cell Transplantation Improves Motor Function in a Mouse Model of Type 3 Spinocerebellar Ataxia

Cited by 13 publications

References 56 publications

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies

Identifying Therapeutic Targets for Spinocerebellar Ataxia Type 3/Machado–Joseph Disease through Integration of Pathological Biomarkers and Therapeutic Strategies

Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Contact Info

Product

Resources

About