Treatment of Parkinson's disease using cell transplantation

Lindvall, Olle

doi:10.1098/rstb.2014.0370

Cited by 73 publications

(35 citation statements)

References 59 publications

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“…However, better methods of developing more reliable IPSCs have advanced. Grafting of dopaminergic neurons derived from hIPSCs is being tested for translation in the clinics that can be useful for improving motor functions in PD (Lindvall ).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Mitochondrial dysfunction in Parkinson's disease

Bose

Beal

2016

Journal of Neurochemistry

703

482

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Parkinson's disease (PD) is the second most common neurodegenerative disease. About 2% of the population above the age of 60 is affected by the disease. The pathological hallmarks of the disease include the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies that are made of a-synuclein. Several theories have been suggested for the pathogenesis of PD, of which mitochondrial dysfunction plays a pivotal role in both sporadic and familial forms of the disease. Dysfunction of the mitochondria that is caused by bioenergetic defects, mutations in mitochondrial DNA, nuclear DNA gene mutations linked to mitochondria, and changes in dynamics of the mitochondria such fusion or fission, changes in size and morphology, alterations in trafficking or transport, altered movement of mitochondria, impairment of transcription, and the presence of mutated proteins associated with mitochondria are implicated in PD. In this review, we provide a detailed overview of the mechanisms that can cause mitochondrial dysfunction in PD. We bring to the forefront, new signaling pathways such as the retromer-trafficking pathway and its implication in the disease and also provide a brief overview of therapeutic strategies to improve mitochondrial defects in PD.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Mitochondrial dysfunction in Parkinson's disease

Bose

Beal

2016

Journal of Neurochemistry

703

482

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“…The efforts that have captured the most attention for human use have been implantation of fetal mesencephalic tissue and the development of stem cell approaches. These efforts have been the subject of a number of excellent recent reviews, and we would recommend them for greater detail …”

Section: Cell Replacement Approachesmentioning

confidence: 99%

Induction of axon growth in the adult brain: A new approach to restoration in Parkinson's disease

Padmanabhan

Burke

2017

Movement Disorders

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By the time patients with Parkinson's disease (PD) are first diagnosed, they have already suffered substantial and permanent loss of neurons and their axon projections. Although attention has been given to the possibility of making an earlier, premotor diagnosis of the disease, based on a variety of prodromal signs, such as olfactory dysfunction, constipation, and others, it is not yet possible to do so.1 Therefore, for the foreseeable future, there is a compelling need to develop neurorestorative approaches to the disease. Of the many neural systems, both central and peripheral, affected by PD, the best characterized, in terms of the extent of damage at the time of diagnosis by current motor criteria, is the nigrostriatal dopaminergic projection. In the classic literature and authoritative texts, estimates of 80% loss of striatal dopaminergic innervation at disease onset are often given 2,3 and estimates ranging from 50% to 70% have been proposed for loss of substantia nigra (SN) neurons.2-5 A review of more recent quantitative postmortem and imaging studies would suggest that these are overestimates. It is more likely that there is a 50% to 60% loss of striatal innervation and a 30% loss of neurons.6 These discrepancies notwithstanding, there is a consensus that substantial damage has occurred and that the axon projections bear the brunt of pathology at disease onset. The vulnerability of the axonal projection is especially highlighted in the study of Kordower and colleagues 7 who showed that by 4 years duration of the disease the dopaminergic innervation of the striatum is virtually gone. Thus in premotor and early PD it is the axons that take the brunt of injury and they therefore must merit our attention in approaches to restoration. Cell Replacement ApproachesUp until now, all efforts to provide restoration in PD have focused on cell replacement approaches. The first animal experiments were performed more than 40 years ago by placing solid tissue pieces into the striatum or ventricle 8,9 (see Barker and colleagues 10 for an excellent historic review). The rationale for this approach was to provide the striatum with cells that release dopamine and thereby alleviate the motor deficits. The efforts that have captured the most attention for human use have been implantation of fetal mesencephalic tissue and the development of stem cell approaches. These efforts have been the subject of a number of excellent recent reviews, and we would recommend them for greater detail. [10][11][12] Briefly, since the early days of implantation of whole-tissue fragments, the field of transplantation in the treatment of PD has come a very long way. Importantly, the ethical concerns related to the use of human embryonic tissue have been resolved by the discovery of induced pluripotent stem cells (iPSCs). In all likelihood, challenges at the cell biology level, including cell survival, loss of phenotype, and tumorigenesis, will be solvable. However, another set of challenges, not often discussed, will be those at the systems level...

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“…In addition, some research suggests that transplanted cells in PD and proteinopathies could potentially succumb to the same disease process (Cicchetti et al, 2014, Chu and Kordower, 2010). A comprehensive review of neuronal replacement strategies for PD and other disorders is beyond the scope of this mini-review and several existing reviews provide an excellent assessment of this approach and current clinical perspectives (Barker et al, 2013, Lindvall, 2015). Instead, we focus specifically on those studies that have examined the potential role of NSC-derived neurotrophins in stem cell mediated functional recovery.…”

Section: Neurotrophins and Parkinson’s Diseasementioning

confidence: 99%

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

Marsh

Blurton‐Jones

2017

Neurochemistry International

153

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Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease currently affect tens of millions of people worldwide. Unfortunately, as the world’s population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing.

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Treatment of Parkinson's disease using cell transplantation

Cited by 73 publications

References 59 publications

Mitochondrial dysfunction in Parkinson's disease

Mitochondrial dysfunction in Parkinson's disease

Induction of axon growth in the adult brain: A new approach to restoration in Parkinson's disease

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

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