For this reason, several limiting challenges are still being faced in turning fetal VM grafts into a comparative treatment option for PD. However, two double-blind, placebo-controlled clinical trials failed to meet their primary endpoint, and the overall results obtained from all trials were fairly inconsistent, both between and within trials. With this background, several groups were able to conduct open label clinical trials in PD patients, providing proof of principle that hfVM grafts can be an efficient and safe treatment option for PD. Preclinical studies performed in the 1970s and 1980s in animal models of PD demonstrated that DAn obtained from the fetal midbrain were able to survive transplantation in animal models of PD, integrate into host tissue, release dopamine and improve motor function. These grafts contain immature midbrain DAn and their progenitors, which are generally transplanted into the striatum (the target region of nigral DAn) where they are expected to release and replenish dopamine levels. Transplants of human fetal ventral mesencephalic (hfVM) tissue have been developed in clinic for more than 30 years for PD treatment. Transplants of human fetal ventral mesencephalic tissue Here we summarize general approaches for experimental and clinical applications of stem cell therapy, discussing the common issues, different strategies and how they are being developed as a possible treatment option for PD. įor this reason, alternative treatment options are currently being investigated, among them is particularly interesting the cell replacement therapy (CRT). They are not reparative of basal ganglia circuitry, nor capable of stopping the disease from progressing. Most importantly, these treatments are not a cure. With time, however, these treatments cease to be effective, and some of them are known to develop unpleasant side effects, such as dyskinesias. These include medications in the form of the dopamine precursor levodopa (L-dopa), dopaminergic agonists, or inhibitors of dopamine breakdown (catechol-O-methyl transferase and monoamine oxidase inhibitors) or surgical procedures such as deep brain stimulation (DBS). ![]() Ī variety of treatment options are available to help manage motor symptoms. These may include the loss of trophic support, excessive release of oxygen free radicals, a dysfunctional mechanism of protein degradation, abnormal kinase activity and impairment of mitochondrial function. Although the precise etiology of PD is still unknown, a variety of pathogenic mechanisms have been proposed. ![]() However, the pathology of PD is now known to extend beyond the nigrostriatal dopaminergic pathway itself, leading to a number of secondary motor and non-motor symptoms that can be just as debilitating. The loss of SNpc DAn triggers the recognizable primary motor symptoms, including tremor, rigidity and bradykinesia. In addition, PD patients present with the deposition of α-synuclein-positive protein aggregates called Lewy bodies and neuro-inflammation in various brain regions, further contributing to the progression of the disease. Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the loss of dopamine-producing neurons (DAn) in the substantia nigra pars compacta (SNpc). Stem cells, cell therapy, dopamine neurons, Parkinson’s disease, neurodegeneration. In this review we provide an overview of the different types of human stem cells currently available, mainly multipotent and pluripotent stem cells, their advantages and disadvantages from an experimental and clinical point of view, and how they are being developed clinically for PD treatment. However, the lack of availability of tissue and ethical issues limit the clinical use on a large scale of this strategy, therefore being sought alternative cell sources, based on the use of human stem cells. ![]() Several open label clinical trials involving the intrastriatal transplantation of human fetal ventral mesencephalic tissue (hfVM) has provided proof of concept that CRT could be beneficial for some patients, providing relief of motor symptoms. For this reason, alternative treatment options are being sought in the form of cell replacement therapies (CRT). Current treatment options for PD are available to help relieve primary motor symptoms, but their long-term effectiveness is limited and they do not stop neuronal degeneration. The progressive loss of dopamine neurons (DAn) in the substantia nigra is the main characteristic of Parkinson's disease (PD), the second most common neurodegenerative disorder causing several motor symptoms.
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