Noninvasive, Targeted, and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson's Disease.
Ching Hsiang Fan,Chien Yu Ting,Chung Yin Lin,Hong-Lin Chan,Yuan-Chih Chang,You Yin Chen,Hao-Li Liu,Chih-Kuang Yeh +7 more
TLDR
It is demonstrated that the focused ultrasound-triggered GDNFp-loaded cationic microbubbles platform can achieve non-viral targeted gene delivery via a noninvasive administration route, outperform intracerebral injection in terms of targeted GDNF delivery of high-titer GDNF genes, and has a neuroprotection effect in Parkinson’s disease animal models.Abstract:
Glial cell line-derived neurotrophic factor (GDNF) supports the growth and survival of dopaminergic neurons. CNS gene delivery currently relies on invasive intracerebral injection to transit the blood-brain barrier. Non-viral gene delivery via systematic transvascular route is an attractive alternative because it is non-invasive, but a high-yield and targeted gene-expressed method is still lacking. In this study, we propose a novel non-viral gene delivery approach to achieve targeted gene transfection. Cationic microbubbles as gene carriers were developed to allow the stable formation of a bubble-GDNF gene complex, and transcranial focused ultrasound (FUS) exposure concurrently interacting with the bubble-gene complex allowed transient gene permeation and induced local GDNF expression. We demonstrate that the focused ultrasound-triggered GDNFp-loaded cationic microbubbles platform can achieve non-viral targeted gene delivery via a noninvasive administration route, outperform intracerebral injection in terms of targeted GDNF delivery of high-titer GDNF genes, and has a neuroprotection effect in Parkinson's disease (PD) animal models to successfully block PD syndrome progression and to restore behavioral function. This study explores the potential of using FUS and bubble-gene complexes to achieve noninvasive and targeted gene delivery for the treatment of neurodegenerative disease.read more
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An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications.
TL;DR: The underlying principles of HIFU are reviewed and current applications, outcomes, and complications after treatment are presented and recent applications of Focused ultrasound for tumor treatment, drug delivery, vessel occlusion, histotripsy, movement disorders, and vascular, oncologic, and psychiatric applications are reviewed.
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Applications of focused ultrasound in the brain: from thermoablation to drug delivery.
TL;DR: The potential impact of FUS on the landscape of brain therapies as well as the challenges facing further advancement and broader adoption of this promising minimally invasive therapeutic alternative are examined.
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A Review of Low-Intensity Pulsed Ultrasound for Therapeutic Applications
TL;DR: An overview of the recent developments of LIPUS for therapeutic applications is provided, based on the papers that report positive effects, and the findings on the understanding of its mechanism are presented.
Journal ArticleDOI
Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy.
Nisi Zhang,Fei Yan,Xiaolong Liang,Manxiang Wu,Manxiang Wu,Yuanyuan Shen,Min Chen,Yunxue Xu,Guangyang Zou,Peng Jiang,Caiyun Tang,Hairong Zheng,Zhifei Dai +12 more
TL;DR: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.
Journal ArticleDOI
Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson's disease mouse model.
Chung Yin Lin,Chung Yin Lin,Han Yi Hsieh,Chiung Mei Chen,Shang Rung Wu,Chih-Hung Tsai,Chiung Yin Huang,Mu-Yi Hua,Kuo Chen Wei,Chih-Kuang Yeh,Hao-Li Liu +10 more
TL;DR: It is suggested that FUS exposures with the administration of LpDNA-MBs complexes synergistically can serve as an effective gene therapy strategy for MPTP-animal treatment, and may have potential for further application to perform gene therapy for neurodegenerative disease.
References
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Journal ArticleDOI
GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons
TL;DR: In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.
Journal ArticleDOI
Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.
Kenneth A. Follett,Kenneth A. Follett,Frances M. Weaver,Matthew B. Stern,Kwan Hur,Crystal L. Harris,Ping Luo,William J. Marks,Johannes C. Rothlind,Oren Sagher,Claudia S. Moy,Rajesh Pahwa,Kim J. Burchiel,Kim J. Burchiel,Penelope Hogarth,Eugene C. Lai,John E. Duda,Kathryn L. Holloway,Ali Samii,Stacy Horn,Jeff M. Bronstein,Gatana Stoner,Philip A. Starr,Richard K. Simpson,Gordon H. Baltuch,Antonio A.F. De Salles,Grant D. Huang,Domenic J. Reda +27 more
TL;DR: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation, and nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation.
Journal ArticleDOI
Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo
TL;DR: It is concluded that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.
Journal ArticleDOI
Functional recovery in parkinsonian monkeys treated with GDNF.
Don M. Gash,Zhiming Zhang,Aliza Ovadia,Wayne A. Cass,Ai Yi,Linda A. Simmerman,D Russell,David W. Martin,Paul A. Lapchak,Frank H. Collins,B J Hoffer,Greg A. Gerhardt +11 more
TL;DR: Evaluating the effects of GDNF injected intracerebrally into rhesus monkeys that have had the symptomatology and pathophysiological features of Parkinson's disease induced by the neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine indicates that GDNF may be of benefit in the treatment of Parkinson’s disease.
Journal ArticleDOI
Overcoming the blood-brain tumor barrier for effective glioblastoma treatment
O. van Tellingen,B. Yetkin-Arik,M.C. de Gooijer,Pieter Wesseling,Pieter Wesseling,Thomas Wurdinger,Thomas Wurdinger,H.E. de Vries +7 more
TL;DR: Methods to overcome the blood-brain tumor barrier barrier (BBTB) are provided, including osmotic blood- brain barrier disruption (BBBD), bradykinin receptor-mediated BBTB opening, inhibition of multidrug efflux transporters, receptor- mediated transport systems and physiological circumvention of the BBTB.