Treating non-motor symptoms of Parkinson’s disease with transplantation of stem cells

Abstract

Summary Parkinson’s disease (PD) treatment-based research has focused on developing therapies for the management of motor symptoms. Non-motor symptoms do not respond to treatments targeting motor deficits, thus necessitating an urgent need to develop new modalities that cater to both motor and non-motor deficits. Stem cell transplantation is potentially therapeutic for PD, but the disease non-motor symptoms have been primarily neglected in such cell therapy regimens. Many types of stem cells are currently available for transplantation therapy, including adult tissue (e.g., bone marrow, placenta)-derived mesenchymal stem cells (MSCs). The fact that MSCs can replace and rescue degenerated dopaminergic, and non-dopaminergic cells suggest their potential for the treatment of motor, as well as non-motor symptoms of PD, which is we discuss here.

Challenges and translational considerations of mesenchymal stem/stromal cell therapy for Parkinson’s disease

“…Due to the selective degeneration of neurons in PD, cell-based therapies including neuronal transplantation were viewed as compelling therapeutic approaches. The proposed mechanisms of cell transplantation that allow for the mitigation of neurodegeneration and symptoms include neurite outgrowth of grafts, graft innervation, and formation of synaptic connections with the host tissue 25 , the expression of tyrosine hydroxylase, the release of dopamine, and the release of neurotrophic and neuroprotective bioactive molecules from the transplanted cells 26,27 .…”

Mesenchymal Stem Cells-derived Exosomes: A New Possible Therapeutic Strategy for Parkinson’s Disease?

“…Therefore, PD is clinically recognized by a core of motor symptoms, including bradykinesia, rigidity, tremor, and postural instability, which are used in the establishment of its diagnosis [6]. However, non-motor symptoms, such as depression, sleep disorders, dementia, and peripheral impairments, have also been linked with functional disabilities, preceding the appearance of the motor symptomatology [7]. Thus, the development of management strategies is crucial, in which the diagnosis and the evaluation of the condition of the patient should be accurate, being followed by the development and application of personalized strategies, aiming to ameliorate the patient’s quality of life [8].…”

Non-Motor Symptoms after One Week of High Cadence Cycling in Parkinson’s Disease

“…It is suggested that high cadence cycling may increase sensory feedback; activating basal ganglia circuits to enhance central motor processing may explain these favorable motor function results. However, it is possible that this approach is favorable for targeting motor symptoms, not non-motor symptoms [46,47,48]. Non-motor symptoms of PD are regulated by multiple non-dopaminergic neurotransmitters; thus, common levodopa and other pharmacological dopamine therapies may not address associated neurotransmitter dysfunction [48,49].…”

“…However, it is possible that this approach is favorable for targeting motor symptoms, not non-motor symptoms [46,47,48]. Non-motor symptoms of PD are regulated by multiple non-dopaminergic neurotransmitters; thus, common levodopa and other pharmacological dopamine therapies may not address associated neurotransmitter dysfunction [48,49]. Interestingly, reports suggest that non-motor symptoms, such as depression, may have an “inconsistent relationship [with the] severity of motor symptoms” [50,51].…”