Advancing Extracellular Vesicle Therapeutics into Clinical Trials for Central Nervous System Disorders

Abstract

In December 2023, the US Food and Drug Administration released a draft guidance document titled “Potency Assurance for Cellular and Gene Therapy Products Draft Guidance for Industry” for public comment [1]. Potency assays are arguably the most problematic analytic release assay to develop for cell and cell derivate products, including Extracellular Vesicles (EV). EVs are produced by many cell types and harbor parent cell-specific bioactive cargoes including proteins and nucleic acids. They are unique intercellular signaling particles that can act as both the messenger and/or effector in recipient cells. We and others have shown that Neural Stem Cell EVs (NSC EVs) derived in bioreactors have therapeutic potential for treating neurological disease and Acute Ischemic Stroke (AIS). New FDA Investigational New Drug (IND) applications are being filed and specifically, we have an IND application for AIS. As the field grows, new INDs will be filed for various other therapeutic indications. In order for EV therapeutics to move efficiently through the regulatory process to approval, there is a need for more emphasis on and development of analytical assays directly related to complex and likely multimodal, mechanisms of action. Research focused on this area will lead to new disease-specific potency assays and identification of critical quality attributes.