Therapeutic potential of extracellular vesicles in neurodegenerative disorders

Neurodegenerative disorders are characterized by complex multifactorial pathogeneses, thus posing a challenge for standard therapeutic approaches that tend to focus only on one underlying disease aspect. For systemically administered drugs, the blood-brain barrier (BBB) is yet another major obstacle to overcome. In this context, naturally occurring extracellular vesicles (EVs) with intrinsic ability to cross the BBB have been investigated as therapeutics for various diseases, including Alzheimer's and Parkinson's diseases. EVs are cell-derived, lipid membrane-enclosed vesicles carrying a broad spectrum of biologically active molecules, which play a crucial role in intercellular communication. In a therapeutic context, mesenchymal stem cell (MSC)-derived EVs are in the spotlight because they reflect the therapeutic properties of their parental cells and, thus, hold promise as independent cell-free therapeutics. On the other hand, EVs can be used as drug delivery vehicles by modifying their surface or content, e.g., by decorating the surface with brain-specific ligands or loading the EVs with therapeutic RNAs or proteins, thus further enhancing the EV's targeting and therapeutic potency, respectively. Although EVs have been deemed safe for use in humans, some obstacles remain that prevent their progression into clinics. This review scrutinizes the promises and challenges of EV-based treatments for neurodegenerative disorders.