Gene Therapy for Parkinson’s Disease: Still a Hot Topic?

Kordower, Jeffrey H.

doi:10.1038/npp.2014.235

Cited by 9 publications

(3 citation statements)

References 6 publications

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“…Currently, symptomatic treatment with drugs that stimulate dopamine receptors is used to treat PD (Kalia and Lang, 2015); however, these drugs have major side effects (Kordower, 2015). To reduce and counteract these effects, traditional Chinese medicine has been studied and applied (Chua et al, 2017;Liu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

Gai

Chai

et al. 2020

Front. Pharmacol.

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As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson’s disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.

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Section: Introductionmentioning

confidence: 99%

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

Gai

Chai

et al. 2020

Front. Pharmacol.

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“…Using foreign nucleic acids to repair defective genes, gene therapy has provided a promising treatment strategy for some severe diseases caused by genetic defects, such as Parkinson's disease [1][2][3] and cancer. 4,5 Introducing genetic materials into target cells, gene therapy requires efficient and safe gene delivery systems without causing any associated pathogenic effects.…”

Section: Introductionmentioning

confidence: 99%

A block copolymer containing PEG and histamine-like segments: well-defined functions for gene delivery

Zhao

Jiayu

et al. 2016

New J. Chem.

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The delivery of genetic materials to cells provides a promising treatment approach to many genetic diseases. The rational structural design for reducing the toxicity while improving transfection efficiency is an important strategy for the development of safe and highly efficient polycation gene vectors. In this study, a novel block copolymer composed of PEG and cationic histamine-like segments was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently the potential of its gene vector was explored in vitro. The block copolymer showed a lower cytotoxicity to three cell lines. After complexation with pEGFP-C1, the resulting DNA-encapsulated micelles possessed uniform small size, high salt and serum tolerance which were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Highly efficient gene transfection was further obtained in human liver carcinoma (HepG2) in vitro. The low cytotoxicity and high transfection stem from the well-defined functions of different moieties, PEG segments, imidazolium and amine groups on histamine-like pendants contributing to the different steps of gene delivery, including colloid stability, highly effective DNA condensation and endosomal escape respectively.

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“…The Ceregene sponsored Neurturin trials failed to meet the primary endpoint of symptomatic relief in Phase II. It has been broadly debated why this happened [12,[18][19][20], was the degeneration of the DA system too severe in the selected patient population? Was the dosage too low or the AAV serotype suboptimal?…”

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confidence: 99%

Repairing the Brain: Gene Therapy

Björklund

2018

JPD

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In vivo gene therapy for neurodegenerative disorders has turned out to be a formidable challenge. It is a field not much older than twenty years, but we were many who would have predicted a much easier path towards the clinic using this treatment modality. For Parkinson's disease patients, this has meant a frustrating wait, seeing many promising therapies being forgotten after a few pre-clinical proof-of-concept studies. The reasons for this are both scientific and economical. However, this is slowly but surely changing and over the next two decades we will see a very exciting development in this field. In a foreseeable future, gene therapy will be a very natural component of many clinical therapies, not least in Parkinson's disease.

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Gene Therapy for Parkinson’s Disease: Still a Hot Topic?

Cited by 9 publications

References 6 publications

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson’s Disease via Parkin

A block copolymer containing PEG and histamine-like segments: well-defined functions for gene delivery

Repairing the Brain: Gene Therapy

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