Abstract

Moving Neural Stem Cell Derived Exosome into Clinical Trials: Manufacturing and Mechanistic Considerations

Steven Stice, Co-Founder and Chief Scientific Officer, Aruna Bio

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 open IND 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. Beyond AIS, one of the most promising applications of NSC EVs is in the treatment of amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disease that affects the motor neurons in the brain and spinal cord. In a preliminary study, we have shown that NSC EVs significantly preserved motor function, decreased serum neurofilament light chain, and prolonged survival in ALS mice. NSC EVs also reduced inflammatory mediators TNFa, IL-1ß, IL-6, RIPK1, and NLRP3 in the lumbar spinal. These results suggest that NSC EVs have the potential to be developed as a therapeutic for ALS. The complex pathogenesis in the central nervous system during ALS suggests the need to develop drugs with multimodal therapeutic action and will likely require the development of multiple potency assays relevant to the active agents in and on the surface of the NSC EVs.