Clinically relevant small-molecule promotes nerve repair and visual function recovery

Ngan Pan Bennett Au; Gajendra Kumar; Pallavi Asthana; Fuying Gao; Riki Kawaguchi; Raymond Chuen Chung Chang; Kwok Fai So; Yang Hu; Daniel H Geschwind; Giovanni Coppola; Chi Him Eddie Ma

doi:10.1038/s41536-022-00233-8

Clinically relevant small-molecule promotes nerve repair and visual function recovery

NPJ Regen Med. 2022 Oct 1;7(1):50. doi: 10.1038/s41536-022-00233-8.

Authors

Ngan Pan Bennett Au^#¹, Gajendra Kumar^#¹, Pallavi Asthana^#¹, Fuying Gao², Riki Kawaguchi², Raymond Chuen Chung Chang^{3

4}, Kwok Fai So^{4

5

6}, Yang Hu⁷, Daniel H Geschwind^{8

9}, Giovanni Coppola^{8

9}, Chi Him Eddie Ma¹⁰

Affiliations

¹ Department of Neuroscience, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong SAR.
² Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
³ Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.
⁴ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR.
⁵ Department of Ophthalmology, The University of Hong Kong, Pokfulam, Hong Kong.
⁶ Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
⁷ Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, USA.
⁸ Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁹ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
¹⁰ Department of Neuroscience, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong SAR. eddiema@cityu.edu.hk.

^# Contributed equally.

Abstract

Adult mammalian injured axons regenerate over short-distance in the peripheral nervous system (PNS) while the axons in the central nervous system (CNS) are unable to regrow after injury. Here, we demonstrated that Lycium barbarum polysaccharides (LBP), purified from Wolfberry, accelerated long-distance axon regeneration after severe peripheral nerve injury (PNI) and optic nerve crush (ONC). LBP not only promoted intrinsic growth capacity of injured neurons and function recovery after severe PNI, but also induced robust retinal ganglion cell (RGC) survival and axon regeneration after ONC. By using LBP gene expression profile signatures to query a Connectivity map database, we identified a Food and Drug Administration (FDA)-approved small-molecule glycopyrrolate, which promoted PNS axon regeneration, RGC survival and sustained CNS axon regeneration, increased neural firing in the superior colliculus, and enhanced visual target re-innervations by regenerating RGC axons leading to a partial restoration of visual function after ONC. Our study provides insights into repurposing of FDA-approved small molecule for nerve repair and function recovery.

Abstract

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