Extracellular Vesicles in the Treatment of Parkinson’s Disease: A Review
Authors: Yang Xiaoxiao , Ma Yifan , Xie Haotian , Dong Shiyan , Rao Gaofeng , Yang Zhaogang , Zhang Jingjing , Wu Qingqing 
Published: January 2021

Background:
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.

Objective:
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.

Methods:
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.

Conclusion:
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.