TY - JOUR
T1 - Peripherally delivered Adeno-Associated Viral Vectors for spinal cord injury repair
AU - Sydney-Smith, Jared
AU - Barroso Spejo, Aline
AU - Warren, Philippa
AU - Moon, Lawrence D F
N1 - Funding Information:
The authors were funded by Spinal Research (NRB117; JDS-S and LDFM), the King's Prize Fellowship (PMW), Brain Research UK (201617–04 to LDFM for ABS) and the Medical Research Council (MR/S026053/1 to LDFM; MR/S011110/1 to PMW; ABS supported by MR /V002783/1 to Prof. Liz Bradbury).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/2
Y1 - 2022/2
N2 - Via the peripheral and autonomic nervous systems, the spinal cord directly or indirectly connects reciprocally with many body systems (muscular, intengumentary, respiratory, immune, digestive, excretory, reproductive, cardiovascular, etc). Accordingly, spinal cord injury (SCI) can result in catastrophe for multiple body systems including muscle paralysis affecting movement and loss of normal sensation, as well as neuropathic pain, spasticity, reduced fertility and autonomic dysreflexia. Treatments and cure for an injured spinal cord will likely require access of therapeutic agents across the blood-CNS (central nervous system) barrier. However, some types of repair within the CNS may be possible by targeting treatment to peripherally located cells or by delivering AAVs by peripheral routes (e.g., intrathecal, intravenous). This review will consider some future possibilities for spinal cord injury repair generated by therapeutic peripheral gene delivery. There are now six gene therapies approved worldwide as safe and effective medicines of which three were created by modification of the apparently nonpathogenic Adeno-Associated Virus. One of these Adeno-Associated Viral vectors (AAVs), Zolgensma, is injected intrathecally for treatment of spinal muscular atrophy in children. One day, delivery of AAVs into peripheral tissues might improve recovery after spinal cord injury in humans; we discuss experiments by us and others delivering transgenes into nerves or muscles for sensorimotor recovery including human Neurotrophin-3. We also describe ongoing efforts to develop AAVs that are delivered to particular targets within and without the CNS after peripheral administration using capsids with improved tropisms, promoters that are selective for particular cell types, and methods for controlling the dose and duration of expression of a transgene. In conclusion, in the future, minimally invasive administration of AAVs may improve recovery after SCI with minimal side effects.
AB - Via the peripheral and autonomic nervous systems, the spinal cord directly or indirectly connects reciprocally with many body systems (muscular, intengumentary, respiratory, immune, digestive, excretory, reproductive, cardiovascular, etc). Accordingly, spinal cord injury (SCI) can result in catastrophe for multiple body systems including muscle paralysis affecting movement and loss of normal sensation, as well as neuropathic pain, spasticity, reduced fertility and autonomic dysreflexia. Treatments and cure for an injured spinal cord will likely require access of therapeutic agents across the blood-CNS (central nervous system) barrier. However, some types of repair within the CNS may be possible by targeting treatment to peripherally located cells or by delivering AAVs by peripheral routes (e.g., intrathecal, intravenous). This review will consider some future possibilities for spinal cord injury repair generated by therapeutic peripheral gene delivery. There are now six gene therapies approved worldwide as safe and effective medicines of which three were created by modification of the apparently nonpathogenic Adeno-Associated Virus. One of these Adeno-Associated Viral vectors (AAVs), Zolgensma, is injected intrathecally for treatment of spinal muscular atrophy in children. One day, delivery of AAVs into peripheral tissues might improve recovery after spinal cord injury in humans; we discuss experiments by us and others delivering transgenes into nerves or muscles for sensorimotor recovery including human Neurotrophin-3. We also describe ongoing efforts to develop AAVs that are delivered to particular targets within and without the CNS after peripheral administration using capsids with improved tropisms, promoters that are selective for particular cell types, and methods for controlling the dose and duration of expression of a transgene. In conclusion, in the future, minimally invasive administration of AAVs may improve recovery after SCI with minimal side effects.
UR - http://www.scopus.com/inward/record.url?scp=85120989341&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2021.113945
DO - 10.1016/j.expneurol.2021.113945
M3 - Article
SN - 0014-4886
VL - 348
JO - Experimental Neurology
JF - Experimental Neurology
M1 - 113945
ER -
