Extracellular Vesicles in the Treatment of Parkinson's Disease: A Review.

Abstract

Parkinson's disease (PD) is one of the most common neurological disorders that can severely affect the ability to perform daily activities. The clinical presentation of PD includes motor and nonmotor symptoms. The motor symptoms generally involve movement conditions like tremors, rigidity, slowness, and impaired balance. In contrast, the nonmotor symptoms are often not apparent but can affect various organ systems, such as the urinary and gastrointestinal systems, and mental health. Gene mutations and toxic environmental factors have contributed significantly to PD; nevertheless, its cause and underlying mechanism remain unknown. Currently, treatments such as dopamine agonists, RNA molecules, and antioxidants can, to some extent, alleviate the motor symptoms triggered by PD. However, these medicines cannot effectively halt ongoing dopaminergic damage, mainly because the blood-brain barrier (BBB) lowers the efficiency of drug delivery. Recently, extracellular vesicles (EVs), a novel drug delivery platform, have been widely used in various neurological diseases, including stroke and brain tumors, because of their excellent biocompatibility, their ability to penetrate the BBB without toxicity, and their target specificity. EVs thus provide a promising therapeutic for treating PD. This review focuses on novel therapies based on EVs in practice. Herein, we briefly introduce the biogenesis, composition, isolation, and characterization of EVs, and we discuss strategies for loading therapeutic agents onto EVs and recent applications for PD treatment. Moreover, we discuss perspectives on the direction of preclinical and clinical studies regarding novel and effective therapies. A literature search regarding PD treatment based on extracellular vesicles was performed in PubMed (updated in June 2020). Treatment, therapy, drug delivery, extracellular vesicles, and their combinations were the search queries. Both systematic reviews and original publications were included. Searched results were selected and compared based on relevance. Articles published in the last five years were given top priority. PD is a heterogeneous disease that can be treated by using pharmacologic approaches (e.g. dopamine agonists and levodopa) and nonpharmacologic approaches (e.g. music), based on symptoms and progression level in patients. Even though current treatments have demonstrated effectiveness, clinical challenges remain because the BBB reduces the medication received and lowers the efficacy of drug delivery, which impairs the treatment's effect. Therefore, EVs, as an emerging delivery platform, are highly promising for PD treatment since they can readily cross the BBB with high therapeutic efficiency through the loading or functionalization process. However, defining a safe source of EVs, reliably purifying and isolating EVs with high yield, and improving the efficacy of therapeutic loading in EVs remain challenging in this field. Therefore, future investigations should focus on generating large-scale exosomal carriers and designing new effective drugs encapsulated in EVs for better efficacy.