John Garner

PLGA-PEG-PLGA Thermogel from PolySciTech Used in Development of Spinal Cord Injury Treatment

Blog Post created by John Garner on Dec 3, 2019

Traumatic injuries to the spinal column typically occur due to trauma (vehicular/sports accident) which damages or severs the nerves in the spine. Since neural tissue does not repair itself the same way as other tissues, many of these injuries result in a lifetime of paralysis. Recently, researchers at New York University School of Medicine and Qingdao University (China) used PLGA-PEG-PLGA thermogel (AK097) from PolySciTech (www.polyscitech.com) to create a Atsttrin (a progranulin (PGRN) derivative) delivery gel for treatment of spinal cord injury. This research holds promise to repair neural damage and may potentially be used as part of treatment for injury induced paralysis. Read more: Wang, Chao, Lu Zhang, Jean De La Croix Ndong, Aubryanna Hettinghouse, Guodong Sun, Changhong Chen, Chen Zhang, Ronghan Liu, and Chuan-ju Liu. "Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice." Journal of Neuroinflammation 16, no. 1 (2019): 1-12. https://link.springer.com/article/10.1186/s12974-019-1630-1

 

“Abstract: Purpose: Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI. Methods: PGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins. Results: After SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury. Grn−/− mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated that Grn−/− mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency. Conclusion: PGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury. Keywords: Progranulin Inflammation Apoptosis Spinal cord injury”

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