Progress in studies of gene therapy for Huntington's disease
Huntington's disease (HD) is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT ⁃15 involving the expansion of a trinucleotide (CAG) repeat encoding glutamine, which leads to abnorm...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tianjin Huanhu Hospital
2012-06-01
|
| Series: | Chinese Journal of Contemporary Neurology and Neurosurgery |
| Subjects: | |
| Online Access: | http://www.cjcnn.org/index.php/cjcnn/article/view/327 |
| _version_ | 1818318574758920192 |
|---|---|
| author | Fan⁃ying JIN Bao⁃rong ZHANG |
| author_facet | Fan⁃ying JIN Bao⁃rong ZHANG |
| author_sort | Fan⁃ying JIN |
| collection | DOAJ |
| description | Huntington's disease (HD) is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT ⁃15 involving the expansion of a trinucleotide (CAG) repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt) protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT ⁃15 via RNA interference (RNAi) or antisense oligonucleotide (ASO) has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral⁃mediated delivery of anti⁃Htt intrabodies (iAbs) or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF) and brain ⁃ derived neurotrophic factor (BDNF), mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene⁃modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials.
DOI：10.3969/j.issn.1672⁃6731.2012.03.003 |
| first_indexed | 2024-12-13T09:55:23Z |
| format | Article |
| id | doaj.art-9119ec59d7ea4689ad813e465b0a2946 |
| institution | Directory Open Access Journal |
| issn | 1672-6731 |
| language | English |
| last_indexed | 2024-12-13T09:55:23Z |
| publishDate | 2012-06-01 |
| publisher | Tianjin Huanhu Hospital |
| record_format | Article |
| series | Chinese Journal of Contemporary Neurology and Neurosurgery |
| spelling | doaj.art-9119ec59d7ea4689ad813e465b0a29462022-12-21T23:51:48ZengTianjin Huanhu HospitalChinese Journal of Contemporary Neurology and Neurosurgery1672-67312012-06-01123238244326Progress in studies of gene therapy for Huntington's diseaseFan⁃ying JINBao⁃rong ZHANGHuntington's disease (HD) is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT ⁃15 involving the expansion of a trinucleotide (CAG) repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt) protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT ⁃15 via RNA interference (RNAi) or antisense oligonucleotide (ASO) has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral⁃mediated delivery of anti⁃Htt intrabodies (iAbs) or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF) and brain ⁃ derived neurotrophic factor (BDNF), mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene⁃modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials. DOI：10.3969/j.issn.1672⁃6731.2012.03.003http://www.cjcnn.org/index.php/cjcnn/article/view/327Huntington diseaseGene therapyRNA interferenceReview |
| spellingShingle | Fan⁃ying JIN Bao⁃rong ZHANG Progress in studies of gene therapy for Huntington's disease Chinese Journal of Contemporary Neurology and Neurosurgery Huntington disease Gene therapy RNA interference Review |
| title | Progress in studies of gene therapy for Huntington's disease |
| title_full | Progress in studies of gene therapy for Huntington's disease |
| title_fullStr | Progress in studies of gene therapy for Huntington's disease |
| title_full_unstemmed | Progress in studies of gene therapy for Huntington's disease |
| title_short | Progress in studies of gene therapy for Huntington's disease |
| title_sort | progress in studies of gene therapy for huntington s disease |
| topic | Huntington disease Gene therapy RNA interference Review |
| url | http://www.cjcnn.org/index.php/cjcnn/article/view/327 |
| work_keys_str_mv | AT fanyingjin progressinstudiesofgenetherapyforhuntingtonsdisease AT baorongzhang progressinstudiesofgenetherapyforhuntingtonsdisease |