Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

Tomishima, Mark; Kirkeby, Agnete

doi:10.3233/jpd-212685

Cited by 14 publications

(11 citation statements)

References 48 publications

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“…PD is one of the most frequent chronic neurodegenerative disorder affecting aged people [99,100]. This pathophysiological condition, either sporadic or familial, is characterized by the progressive degeneration of striatal-projecting midbrain dopaminergic neurons of the ventral forebrain, resulting in a reduced level of dopamine (DA) in the striatum area, leading to both motor symptoms, such as bradykinesia, rigidity, resting tremor, and postural instability, and cognitive alterations, including depression, dementia, hallucinosis, and sleep and sensory disorders [99,101].…”

Section: Stem Cell Therapy In Pdmentioning

confidence: 99%

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Bonaventura

Munafò

Bellanca

et al. 2021

Cells

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Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s disease).

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Section: Stem Cell Therapy In Pdmentioning

confidence: 99%

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Bonaventura

Munafò

Bellanca

et al. 2021

Cells

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“…Therefore, there is an urgent unmet medical need for the identification and development of novel and effective therapies to treat this disease. Several experimental approaches are being used to achieve these goals like gene therapy, immunotherapy, the use of neurotrophic factors, stem cell therapy, and the design of high-throughput screening (HTS) platforms and drug repurposing strategies, − among others. In this scenario, we have recently performed an in vivo HTS assay aimed to identify new potential candidate compounds to treat PD, using a Drosophila model of the disease based on inactivation of the DJ-1β gene (the fly ortholog of human DJ-1 , a gene involved in familial PD cases) …”

Section: Introductionmentioning

confidence: 99%

Disease-Modifying Effects of Vincamine Supplementation in Drosophila and Human Cell Models of Parkinson’s Disease Based on DJ-1 Deficiency

Sanz

Solana-Manrique

Paricio

2023

ACS Chem. Neurosci.

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Parkinson's disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Current therapies are only symptomatic and are not able to stop or delay its progression. In order to search for new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds that are able to improve locomotor ability in DJ-1β mutant flies (a Drosophila model of familial PD) and reduce oxidative stress (OS)-induced lethality in DJ-1-deficient SH-SY5Y human cells. One of them was vincamine (VIN), a natural alkaloid obtained from the leaves of Vinca minor. Our results showed that VIN is able to suppress PD-related phenotypes in both Drosophila and human cell PD models. Specifically, VIN reduced OS levels in PD model flies. Besides, VIN diminished OSinduced lethality by decreasing apoptosis, increased mitochondrial viability, and reduced OS levels in DJ-1-deficient human cells. In addition, our results show that VIN might be exerting its beneficial role, at least partially, by the inhibition of voltage-gated sodium channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD and that VIN represents a potential therapeutic treatment for the disease.

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“…Cell therapies involve the transplantation of live cells into the brain, using of preparations rich in DA progenitors, with the aim of replacing the lost DA neurons and restoring the nigrostriatal DAergic synapse. The proof-of-concept in this field was established using fetal DA cells, but current trials typically use human embryonic or induced pluripotent stem cells, which have been differentiated towards a DAergic fate (for comprehensive reviews, see [2][3][4][5][6]). Some gene therapy approaches involve the infusion of viral vectors into the caudate-putamen that express genes necessary for the biosynthesis of DA.…”

Section: Introductionmentioning

confidence: 99%

Can cell and gene therapies improve cognitive symptoms in Parkinson’s disease?

Lelos¹

2022

J. Integr. Neurosci.

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Advanced therapeutic medicinal products (ATMPs), including cell and gene therapies, are in development for Parkinson's disease (PD). In many cases, the goal is to replace the lost dopamine (DA), which is anticipated to improve motor dysfunctions associated with DA loss. However, it is less clear the extent to which these therapeutic interventions may impact on the wide range of cognitive symptoms that manifest as the disease progresses. Although the accepted perception is that cognitive symptoms are predominately non-DAergic in origin, in this commentary, it is argued that several, specific cognitive processes, such as habit formation, working memory and reward processing, have been reported to be DA-dependent. Furthermore, there is evidence of DAergic medications modulating these behaviours in PD patients. Finally, the potential for cell and gene ATMPs to influence these symptoms is considered. It is concluded that DA replacement through ATMPs is likely to improve certain DA-dependent symptoms, but only sparse clinical data are currently available and the ability to precisely titrate DA transmission is likely to be complex.

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Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

Cited by 14 publications

References 48 publications

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Disease-Modifying Effects of Vincamine Supplementation in Drosophila and Human Cell Models of Parkinson’s Disease Based on DJ-1 Deficiency

Can cell and gene therapies improve cognitive symptoms in Parkinson’s disease?

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