ExoPTEN: Allogeneic Exosome Therapy for Spinal Cord Injury with Strong Therapeutic Potential and Clinical Promise

Background & Aim

NurExone's ExoPTEN, an exosome-based therapy, represents a novel approach for treating spinal cord injury (SCI). This allogeneic, off-the-shelf therapy utilizes exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) to deliver a proprietary siRNA targeting PTEN, a key inhibitor in the mTOR pathway. With a scalable and robust manufacturing process, ExoPTEN demonstrates significant therapeutic potential, backed by comprehensive preclinical data and strong regulatory achievements, including orphan drug designation (ODD) and supportive pre-IND feed back.

Methodology

Preclinical studies were conducted using two rat models of SCI: complete spinal cord transection and spinal cord compression. ExoPTEN, loaded with siRNA-PTEN, was administered via intranasal and intrathecal routes. Efficacy was evaluated through MRI, BBB motor scoring, von Frey sensory tests, and immunohistochemistry to assess motor, sensory, and structural recovery. The homing capacity of ExoPTEN was evaluated by tracking fluorescently labeled exosomes in rats. Scalability was evaluated by transitioning production from 2D culture systems to 3D bioreactors.

Results

ExoPTEN treatment led to significant improvement in motor and sensory functions in SCI rats, as well as structural recovery. Fluorescent labeling confirmed that ExoPTEN successfully homed to the injury site and remained there up to seven days post-injury, establishing a therapeutic window. Process robustness was maintained throughout the scalability from 2D to 3D production, with consistent exosome yields and functionality across different BM donors and siRNA sources. The positive preclinical data, along with orphan drug designation and supportive pre-IND feedback from the FDA, confirm ExoPTEN's potential for clinical translation.

Conclusion

ExoPTEN offers a groundbreaking therapeutic option for SCI, backed by robust preclinical data, a demonstrated seven-day therapeutic window, and regulatory support. This scalable, and versatile therapy is designed for clinical use, with the ability to load various therapeutic payloads and provide long-term treatment through repeated administration. These encouraging results demonstrate ExoPTEN's clinical potential and its applicability in additional nerve regeneration conditions.