Researchers develop new exosome-based therapeutics to treat traumatic CNS damage

Traumatic injuries to the central nervous system (CNS), such as traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), are characterized by oxidative damage and neuroinflammation. Current treatment relies primarily on supportive care and surgical interventions, resulting in a lack of effective drugs that directly target underlying damage.

For example, neural stem cell (NSC)-based therapy has shown therapeutic potential, but the pathological microenvironment has a negative effect on NSC survival and supervisory differentiation, impairing treatment outcomes. Similarly, successful antioxidant treatments are limited as most antioxidants do not pass efficiently through the blood-brain barrier (BBB).

However, now researchers at the Institute of Process Engineering (IPE) at the Chinese Academy of Sciences have collaborated with Shenzhen Second Person Hospital to develop a new exosome-based therapeutic agent for treating traumatic CNS injuries. This treatment relieves neuronal apoptosis, restores glial homeostasis, modifies glial neural networks, and offers powerful therapeutic benefits in mouse (mouse) TBI and SCI models.

This study was published in Cell Reports Medicine.

Understand that NSC therapy involves intercellular communication via exosome nano-formed vesicles secreted by cells containing NSCs. The researchers proposed using NSC-derived exosomes (NEXO) to treat CNS damage.

The researchers also understood that exosome-based therapy is necessary to address oxidative damage caused by reactive oxygen species (ROS) in the microenvironment.

Inspired by Selenium’s ability to remove ROS, researchers have developed an advanced Nexo containing ultra-exaggerated nanoselenium (~3.5 nm) via lipid-mediated nucleation (Senexo).

Professor Ma Guanghui of IPE said that Senexo invaded the BBB via APOE_LRP-1 interaction after intravenous injection. Upon efficient reaching the lesion site, ultra-flattering nanoselenium effectively removed ROS, and Nexo promoted neuronal repair.

In the mouse TBI model, Senexo reduced brain lesions and improved spatial learning and memory function. Through proteomics, miRNA omics, and single-nuclear RNA sequencing, the researchers demonstrated that Senexo significantly downregulated the expression of genes associated with neuronal oxidative stress and apoptosis. Furthermore, Senexo significantly altered the transcriptional programme of the inflammatory response, promoting glial cells against homeostasis. Additionally, Senexo strengthened neuron-glyarygand receptor pairs involved in CNS development, suppressing inflammation and those associated with the star retina. In the mouse SCI model, Senexo also promoted motor recovery.

Professor Tan Hui of Shenzhen Children’s Hospital and Li Weiping of Shenzhen Second People’s Hospital support the concept that Senexo is a novel and promising therapeutic agent for treating traumatic CNS injuries.

One reviewer at Cell Report Medicine said the study provided compelling evidence that Senexo can protect the brain following TBI and potentially SCI.

Professor Wei Wei of IPE said that Senexo offers excellent biocompatibility and stability. He also said its strong therapeutic efficacy and safety highlights the potential for promising translation to develop clinically relevant CNS injury treatments.