Cell Therapy for Parkinson’s Disease: New Hope from Reprogramming Technologies

Abstract

. The major pathology of PD is the progressive degeneration of dopaminergic (DA) neurons located at the substantia nigra in midbrain, which send axonal projections to striatum and are involved in the circuits controlling motor functions. In addition to motor symptoms caused by degeneration of DA neurons, many PD patients also present with non-motor symptoms, such as cognitive impairment and mood problems [3].To date, no disease modifying treatments exist in clinics. The current treatments mostly target the symptoms only. Pharmaceutical drugs, such as levodopa, catechol-O-methyl transferase, and monoamine oxidase inhibitors, aim at replenishing or stabilizing dopamine supply in striatum; Deep brain stimulation (DBS) normally works by electrically lesioning subthalamic nucleus (STN) or globus pallidus interna (GPi) to increase the collective motor output. However, neither of the above can stop nor reverse the progress of DA neuron degeneration in midbrain. Other emerging treatments that have gone through clinical trials include gene therapies and cell transplantation therapies. Through gene therapy, viral vectors encoding GAD, neurotrophic/growth factors, or enzymes sufficient for production of dopamine have been trialled or still underway [4][5][6][7][8][9]. In this short review, I will focus more on the cell therapy aspect of PD treatment.

Combining NT3-overexpressing MSCs and PLGA microcarriers for brain tissue engineering: A potential tool for treatment of Parkinson's disease

“…However, the application of gene therapy for induction of nerve growth factors expression has been hindered since the transfected cells lack any physical or biological supports [17,48]. In addition, numbers of cell based therapies have been employed pluripotent embryonic stem cells which are not reliable cell source as they irritate immunoreaction and increase the risk of tumor formation [11].…”

“…The methods based on the former prevent the dopaminergic neurons from unwanted death while the latter contributes cell replacement or cell therapy [1]. Cell therapy is considered as an exciting therapeutic method for repair of defected site in the brain tissue of PD's patients [11]. However, there are several key issues that need to be considered in order to effectively utilize cell therapy including the neuronal cell source and their microenvironment that physically and biologically mimic the host parenchymal tissue [12].…”

Therapeutic Potential of Induced Neural Stem Cells for Parkinson’s Disease

“…The major pathology of PD is the progressive degeneration of DA neurons located in the SN in the midbrain, which send axonal projections to the striatum and are involved in the circuits that control motor functions [ 32 ].…”

Imaging and Quantitative Analysis of the Interstitial Space in the Caudate Nucleus in a Rotenone-Induced Rat Model of Parkinson’s Disease Using Tracer-based MRI

“…Moreover, current treatment of PD is not clinically satisfied, and pharmaceutical drugs offer only time-limited symptomatic relief and become less effective as the disease progresses [ 23 ]. Emerging ISS administrations that involve gene therapies and cell transplantation have shown promise in the treatment of PD [ 24 , 25 ]. ISS administration provides a number of advantages over conventional administration, including bypass of the blood brain barrier, minor systemic toxicity and enhanced efficacy, etc [ 26 ].…”