Restorative cell and gene therapies for Parkinson's disease

Barker, Roger A.; Björklund, Anders

doi:10.1016/b978-0-323-85555-6.00012-6

Cited by 9 publications

(6 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stem cell-derived brain repair for Parkinson's offers the possibility of life-long reconstruction of the degenerated dopaminergic input to the striatum after a single surgical transplant (Barker and Bjorklund, 2023). Relative to fetal tissue transplants, stem cells can provide unlimited numbers of the required phenotype of dopaminergic neurons for allogenic transplantation, with the iPSCs offering the additional potential of autologous transplantation.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Over the intervening decades, numerous preclinical studies and clinical trials provided proofof-principle for the efficacy and safety of cellular brain repair, with fetal dopaminergic grafts demonstrating the ability to survive in the brain, reinnervate the dopamine-depleted striatum, and ameliorate dysfunction/symptoms in Parkinsonian models and patients [reviewed in 1,6].…”

Section: Introductionmentioning

confidence: 99%

“…Over the intervening decades, numerous preclinical studies and clinical trials provided proof-of-principle for the efficacy and safety of cellular brain repair, with fetal dopaminergic grafts demonstrating the ability to survive in the brain, reinnervate the dopamine-depleted striatum, and ameliorate dysfunction/symptoms in Parkinsonian models and patients (reviewed in Bjorklund and Parmar, 2020, Barker and Bjorklund, 2023). However, it also became apparent that this approach had serious limitations associated with the need for human fetal donors including supply, ethical concerns and logistical difficulties, all of which would ultimately preclude this translating to a therapy for patients.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Comini,

Dowd

2024

Preprint

View full text Add to dashboard Cite

Stem cell-based brain repair is a promising emergent therapy for Parkinson's which is based on years of foundational research using human fetal donors as a cell source. Unlike current therapeutic options for patients, this approach has the potential to provide long-term stem cell-derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients. The ultimate clinical success of stem cell-derived brain repair will depend on both the safety and efficacy of the approach, and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain. Because the pre-clinical literature suggests that there is a considerable variability in survival and differentiation between studies, the aim of this systematic review was to assess these parameters in human stem-derived dopaminergic progenitor transplant studies in animal models of Parkinson's. To do so, a defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024. After screening, 76 articles were included in the analysis from which 178 separate transplant studies were identified. From these, graft survival could be assessed in 52 studies and differentiation in 129 studies. Overall, we found that graft survival ranged from <1% to 500% of cells transplanted, with a median of 51% of transplanted cells surviving in the brain; while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%. This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors in order to maximize the therapeutic potential of this approach for patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Comini,

Dowd

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Treatments are tailored to each patient considering the benefits and the side effects, mostly relying on the personal expertise of the neurologist and a trial and error process. Some novel and promising approaches are currently under investigation including stem cell-based treatments [21], gene therapy [22] and therapies with the aim of contrasting α-syn toxic effects by inhibiting α-syn production, increasing the degradation of α-syn aggregates, and reducing the uptake of extracellular α-syn by neighboring cells [23]. Targeted rehabilitative programs for motor function, swallowing difficulty, and speech disorders are assuming an important role in improving the quality of life of pwPD [24].…”

Section: Pd Therapeutic Strategiesmentioning

confidence: 99%

Extracellular Vesicles as Biomarkers for Parkinson’s Disease: How Far from Clinical Translation?

Gualerzi,

Picciolini,

Bedoni

et al. 2024

IJMS

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson’s Research to be USD 52 billion in the United States alone. Currently, no effective cure exists, but available PD medical treatments are based on symptomatic prescriptions that include drugs, surgical approaches and rehabilitation treatment. Due to the complex biology of a PD brain, the design of clinical trials and the personalization of treatment strategies require the identification of accessible and measurable biomarkers to monitor the events induced by treatment and disease progression and to predict patients’ responsiveness. In the present review, we strive to briefly summarize current knowledge about PD biomarkers, focusing on the role of extracellular vesicles as active or involuntary carriers of disease-associated proteins, with particular attention to those research works that envision possible clinical applications.

show abstract

The history and status of dopamine cell therapies for Parkinson's disease

Barker,

Björklund,

Parmar

2024

BioEssays

View full text Add to dashboard Cite

Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell‐derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.

show abstract

Restorative cell and gene therapies for Parkinson's disease

Cited by 9 publications

References 124 publications

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Extracellular Vesicles as Biomarkers for Parkinson’s Disease: How Far from Clinical Translation?

The history and status of dopamine cell therapies for Parkinson's disease

Contact Info

Product

Resources

About