scholarly journals Efficient Gene Therapy for Parkinson's Disease Using Astrocytes as Hosts for Localized Neurotrophic Factor Delivery

2012 ◽  
Vol 20 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Anja Drinkut ◽  
Yuliya Tereshchenko ◽  
Jörg B Schulz ◽  
Mathias Bähr ◽  
Sebastian Kügler
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Neurotrophic Factor ◽  
Efficient Gene

Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy

2020 ◽  
Vol 20 (3) ◽  
pp. 207-222
Author(s):  
Tapan Behl ◽  
Ishnoor Kaur ◽  
Arun Kumar ◽  
Vineet Mehta ◽  
Gokhan Zengin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Viral Vector ◽  
Neurodegenerative Disorder ◽  
Dopamine Synthesis ◽  
Motor Symptoms ◽  
Ligand Complex

: The limitations of conventional treatment therapies in Parkinson’s disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson’s disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson’s disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.

Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease

2005 ◽  
Vol 134 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Jie-Sheng Zheng ◽  
Ling-Ling Tang ◽  
Shu-Sen Zheng ◽  
Ren-Ya Zhan ◽  
Yong-Qing Zhou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Rat Model ◽  
Neurotrophic Factor

Molecular imaging of gene therapy. The future in Parkinson's disease therapy?

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
A.H Jacobs ◽  
R Hilker ◽  
L Burghaus ◽  
W.D Heiss
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Molecular Imaging ◽  
Disease Therapy ◽  
The Future

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals The Parkinson’s Disease Comprehensive Response (PDCORE): a composite approach integrating three standard outcome measures

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Matthias Luz ◽  
Alan Whone ◽  
Niccolò Bassani ◽  
Richard K Wyse ◽  
Glenn T Stebbins ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Rating Scale ◽  
Initial Development ◽  
Disease Rating ◽  
Recent Phase ◽  
Data Source

Abstract There is an increasing need for improved endpoints to assess clinical trial effects in Parkinson’s disease. We propose the Parkinson’s Disease Comprehensive Response as a novel weighted composite endpoint integrating changes measured in three established Parkinson’s outcomes, including: OFF state Movement Disorder Society Unified Parkinson’s Disease Rating Scale Motor Examination scores; Motor Experiences of Daily Living scores; and total good-quality ON time per day. The data source for the initial development of the composite described herein was a recent Phase II trial of glial cell line-derived neurotrophic factor. A wide range of clinically derived relative weights was assessed to normalize for differentially scoring base rates with each endpoint component. The Parkinson’s disease comprehensive response, in contrast to examining practically defined OFF state Unified Parkinson’s Disease Rating Scale Motor Examination scores alone, showed stability over 40 weeks in placebo patients, and all 432 analyses in this permutation exercise yielded significant differences in favour of glial cell line-derived neurotrophic factor. The findings were consistent with results obtained employing three different global statistical test methodologies and with patterns of intra-patient change. Based on our detailed analyses, we conclude it worth prospectively evaluating the clinical utility, validity and regulatory feasibility of using clinically supported final Parkinson’s disease comprehensive response formulas (for both the Unified Parkinson’s Disease Rating Scale-based and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale-based versions) in future disease-modifying Parkinson’s trials. Whilst the data source employed in the initial development of this weighted composite score is from a recent Phase II trial of glial cell line-derived neurotrophic factor, we wish to stress that the results are not described to provide post hoc evidence of the efficacy of glial cell line-derived neurotrophic factor but rather are presented to further the debate of how current regulatory approved rating scales may be combined to address some of the recognized limitations of using individual scales in isolation.

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