scholarly journals An Update on Gene Therapy Approaches for Parkinson’s Disease: Restoration of Dopaminergic Function

2021 ◽  
pp. 1-10
Author(s):  
Amber D. Van Laar ◽  
Victor S. Van Laar ◽  
Waldy San Sebastian ◽  
Aristide Merola ◽  
J. Bradley Elder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Genetic Material ◽  
Unmet Need ◽  
Surgical Approaches ◽  
Nigrostriatal Pathway ◽  
Neuronal Function ◽  
Network Function ◽  
Clinical Gene Therapy

At present there is a significant unmet need for clinically available treatments for Parkinson’s disease (PD) patients to stably restore balance to dopamine network function, leaving patients with inadequate management of symptoms as the disease progresses. Gene therapy is an attractive approach to impart a durable effect on neuronal function through introduction of genetic material to reestablish dopamine levels and/or functionally recover dopaminergic signaling by improving neuronal health. Ongoing clinical gene therapy trials in PD are focused on enzymatic enhancement of dopamine production and/or the restoration of the nigrostriatal pathway to improve dopaminergic network function. In this review, we discuss data from current gene therapy trials for PD and recent advances in study design and surgical approaches.

scholarly journals Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease

2020 ◽  
Vol 91 (11) ◽  
pp. 1210-1218 ◽  
Author(s):  
R Mark Richardson ◽  
Krystof S Bankiewicz ◽  
Chadwick W Christine ◽  
Amber D Van Laar ◽  
Robert E Gross ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Viral Vector ◽  
Data Driven ◽  
Surgical Approaches ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Virus Serotype ◽  
Vector Delivery

Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson’s disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. These challenges have recently been addressed during the evolution of novel techniques for vector delivery that include the use of intraoperative MRI. The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery.

scholarly journals Surgical Management of Parkinson's Disease: Update and Review

2007 ◽  
Vol 13 (4) ◽  
pp. 359-368 ◽  
Author(s):  
Y. Chao ◽  
L. Gang ◽  
Z.L. Na ◽  
W.Y. Ming ◽  
W.S. Zhong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Surgical Approaches ◽  
Internal Globus Pallidus ◽  
Ventral Intermediate Nucleus ◽  
Alternative Approaches ◽  
Deep Brain

Although medical therapy is still the mainstay of treatment for Parkinson's disease, the development of surgical precision and decreased morbidity have made stereotatic lesioning and deep brain stimulation more popular. Neurosurgical ablations include pallidotomy, thalamotomy, and, more recently, subthalamotomy. Because of concern over the high risk of side-effects resulting from bilateral ablative procedure, alternative approaches have been explored. With improved deep brain stimulation (DBS) technology, DBS has been successfully applied in the internal globus pallidus, ventral intermediate nucleus and subthalamic nucleus for Parkinson's disease. In addition, recent surgical approaches including biological neurorestorative technologies — surgical therapies with transplantation, gene therapy, and growth factor are all being discussed in this review. Although a great deal of work remains to be done for researchers, advances in surgical therapies for the treatment of Parkinson's disease are moving forward at an unprecedented pace, and, not surprisingly, would give PD patients more choices and hope.

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 Social listening – revealing Parkinson’s disease over day and night

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Zhang ◽  
Fanwen Meng ◽  
Xingyu Li ◽  
Yali Ning ◽  
Meng Cai
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Unmet Needs ◽  
Unmet Need ◽  
Motor Symptoms ◽  
Motor Complications ◽  
Sentiment Score ◽  
Negative Sentiment ◽  
Non Motor Symptoms ◽  
Social Listening

Abstract Background Nocturnal symptoms in Parkinson’s disease are often treated after management of daytime manifestations. In order to better understand the unmet needs of nocturnal symptoms management, we analyzed the characteristics and burden of nocturnal symptoms from patients’ perspectives and explored their changes over time. Overall symptoms (occurring at day or night) were collected to compare whether the unmet needs related to nocturnal symptoms and to overall symptoms are different. Methods We used a Social Listening big-data technique to analyze large amounts of Parkinson’s disease symptoms in dialogues available from social media platforms in 2016 to 2018. These symptoms were classified as either overall symptoms or nocturnal symptoms. We used share of voice (SOV) of symptoms as a proportion of total dialogues per year to reflect the characteristics of symptoms. Negative sentiment score of symptoms was analyzed to find out their related burden. Results We found the SOV for overall motor symptoms was 79% and had not increased between 2016 and 2018 (79%, p = 0.5). The SOV for non-motor symptoms was 69% and had grown by 7% in 2018 (p <  0.01). The SOV for motor complications was 9% and had increased by 6% in 2018 (p <  0.01). The SOV of motor symptoms was larger than non-motor symptoms and motor complications (p <  0.01). The SOV of non-motor symptoms was larger than motor complications (p <  0.01). For nocturnal symptoms, 45% of the analyzed PD population reported nocturnal symptoms in 2018, growing by 6% (p <  0.01). The SOV for nocturnal-occurring motor symptoms was higher than most non-motor symptoms. However, non-motor symptoms had the higher increases and evoked higher negative sentiment regardless of whether they occurred during the day or night. For symptoms that can occur at either day or night, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom during the day. Conclusions The growing SOV and the greater negative sentiment of nocturnal symptoms suggest management of nocturnal symptoms is an unmet need of patients. A greater emphasis on detecting and treating nocturnal symptoms with 24-h care is encouraged.

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