A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects
Nerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2022.2149055 |
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| author | Yukari Koya Hirotsugu Tanaka Eiji Yoshimi Nobuaki Takeshita Shuji Morita Hiroki Morio Kanako Mori Hiroshi Fushiki Masazumi Kamohara |
| author_facet | Yukari Koya Hirotsugu Tanaka Eiji Yoshimi Nobuaki Takeshita Shuji Morita Hiroki Morio Kanako Mori Hiroshi Fushiki Masazumi Kamohara |
| author_sort | Yukari Koya |
| collection | DOAJ |
| description | Nerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with clinical chronic pain conditions, anti-NGF IgGs are associated with safety concerns such as effects on fetal and postnatal development and the risk of rapidly progressive osteoarthritis. To overcome these drawbacks, we generated a novel anti-NGF PEGylated Fab’ antibody. The anti-NGF PEGylated Fab’ showed specific binding to and biological inhibitory activity against NGF, and analgesic effects in adjuvant-induced arthritis model mice in a similar manner to an anti-NGF IgG. In collagen-induced arthritis model mice, the anti-NGF PEGylated Fab’ showed higher accumulation in inflamed foot pads than the anti-NGF IgG. In pregnant rats and non-human primates, the anti-NGF PEGylated Fab’ was undetectable in fetuses, while the anti-NGF IgG was detected and caused abnormal postnatal development. The PEGylated Fab’ and IgG also differed in their ability to form immune complexes in vitro. Additionally, while both PEGylated Fab’ and IgG showed analgesic effects in sodium monoiodoacetate-induced arthritic model rats, their effects on edema were surprisingly quite different. While the anti-NGF IgG promoted edema over time, the anti-NGF PEGylated Fab’ did not. The anti-NGF PEGylated Fab’ (ASP6294) may thus be a potential therapeutic candidate with lower risk of adverse effects for various diseases in which NGF is involved such as OA and chronic back pain. |
| format | Article |
| id | doaj-art-1d317d9198cb4f5ca6596cc78d7ab4ae |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-1d317d9198cb4f5ca6596cc78d7ab4ae2025-08-20T03:25:59ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2022.2149055A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effectsYukari Koya0Hirotsugu Tanaka1Eiji Yoshimi2Nobuaki Takeshita3Shuji Morita4Hiroki Morio5Kanako Mori6Hiroshi Fushiki7Masazumi Kamohara8Drug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanIncubation Lab, Astellas Innovation Management LLC, Cambridge, MA, USADrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanDrug Discovery Research, Astellas Pharma Inc, Tsukuba, JapanNerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with clinical chronic pain conditions, anti-NGF IgGs are associated with safety concerns such as effects on fetal and postnatal development and the risk of rapidly progressive osteoarthritis. To overcome these drawbacks, we generated a novel anti-NGF PEGylated Fab’ antibody. The anti-NGF PEGylated Fab’ showed specific binding to and biological inhibitory activity against NGF, and analgesic effects in adjuvant-induced arthritis model mice in a similar manner to an anti-NGF IgG. In collagen-induced arthritis model mice, the anti-NGF PEGylated Fab’ showed higher accumulation in inflamed foot pads than the anti-NGF IgG. In pregnant rats and non-human primates, the anti-NGF PEGylated Fab’ was undetectable in fetuses, while the anti-NGF IgG was detected and caused abnormal postnatal development. The PEGylated Fab’ and IgG also differed in their ability to form immune complexes in vitro. Additionally, while both PEGylated Fab’ and IgG showed analgesic effects in sodium monoiodoacetate-induced arthritic model rats, their effects on edema were surprisingly quite different. While the anti-NGF IgG promoted edema over time, the anti-NGF PEGylated Fab’ did not. The anti-NGF PEGylated Fab’ (ASP6294) may thus be a potential therapeutic candidate with lower risk of adverse effects for various diseases in which NGF is involved such as OA and chronic back pain.https://www.tandfonline.com/doi/10.1080/19420862.2022.2149055NGFPEGylated antibodyfabarthritispainplacental transfer |
| spellingShingle | Yukari Koya Hirotsugu Tanaka Eiji Yoshimi Nobuaki Takeshita Shuji Morita Hiroki Morio Kanako Mori Hiroshi Fushiki Masazumi Kamohara A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects mAbs NGF PEGylated antibody fab arthritis pain placental transfer |
| title | A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects |
| title_full | A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects |
| title_fullStr | A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects |
| title_full_unstemmed | A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects |
| title_short | A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects |
| title_sort | novel anti ngf pegylated fab provides analgesia with lower risk of adverse effects |
| topic | NGF PEGylated antibody fab arthritis pain placental transfer |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2022.2149055 |
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