Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis
Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory loss, cognitive decline, and eventually dementia. The etiology of AD and its pathological mechanisms remain unclear due to its complex pathobiology. At the same time, the number of patients with AD is increasing worldwide. Ho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/411 |
| _version_ | 1797477154564341760 |
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| author | Toshihiko Tashima |
| author_facet | Toshihiko Tashima |
| author_sort | Toshihiko Tashima |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory loss, cognitive decline, and eventually dementia. The etiology of AD and its pathological mechanisms remain unclear due to its complex pathobiology. At the same time, the number of patients with AD is increasing worldwide. However, no therapeutic agents for AD are currently available for definitive care. Several phase 3 clinical trials using agents targeting amyloid β (Aβ) and its related molecules have failed, with the exception of aducanumab, an anti-Aβ monoclonal antibody (mAb), clinically approved by the US Food and Drug Administration in 2021, which could be modified for AD drug development due to controversial approval. Neurofibrillary tangles (NFTs) composed of tau rather than senile plaques composed of Aβ are correlated with AD pathogenesis. Moreover, Aβ and tau pathologies initially proceed independently. At a certain point in the progression of AD symptoms, the Aβ pathology is involved in the alteration and spreading of the tau pathology. Therefore, tau-targeting therapies have attracted the attention of pharmaceutical scientists, as well as Aβ-targeting therapies. In this review, I introduce the implementations and potential of AD immunotherapy using intravenously administered anti-tau and anti-receptor bispecific mAbs. These cross the blood-brain barrier (BBB) based on receptor-mediated transcytosis and are subsequently cleared by microglia based on Fc-mediated endocytosis after binding to tau and lysosomal degradation. |
| first_indexed | 2024-03-09T21:13:36Z |
| format | Article |
| id | doaj.art-03c4a2ed3d2c47259efbbd4037e569f4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:36Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-03c4a2ed3d2c47259efbbd4037e569f42023-11-23T21:38:54ZengMDPI AGPharmaceutics1999-49232022-02-0114241110.3390/pharmaceutics14020411Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated TranscytosisToshihiko Tashima0Tashima Laboratories of Arts and Sciences, 1239-5 Toriyama-cho, Kohoku-ku, Yokohama 222-0035, JapanAlzheimer’s disease (AD) is a neurodegenerative disease that causes memory loss, cognitive decline, and eventually dementia. The etiology of AD and its pathological mechanisms remain unclear due to its complex pathobiology. At the same time, the number of patients with AD is increasing worldwide. However, no therapeutic agents for AD are currently available for definitive care. Several phase 3 clinical trials using agents targeting amyloid β (Aβ) and its related molecules have failed, with the exception of aducanumab, an anti-Aβ monoclonal antibody (mAb), clinically approved by the US Food and Drug Administration in 2021, which could be modified for AD drug development due to controversial approval. Neurofibrillary tangles (NFTs) composed of tau rather than senile plaques composed of Aβ are correlated with AD pathogenesis. Moreover, Aβ and tau pathologies initially proceed independently. At a certain point in the progression of AD symptoms, the Aβ pathology is involved in the alteration and spreading of the tau pathology. Therefore, tau-targeting therapies have attracted the attention of pharmaceutical scientists, as well as Aβ-targeting therapies. In this review, I introduce the implementations and potential of AD immunotherapy using intravenously administered anti-tau and anti-receptor bispecific mAbs. These cross the blood-brain barrier (BBB) based on receptor-mediated transcytosis and are subsequently cleared by microglia based on Fc-mediated endocytosis after binding to tau and lysosomal degradation.https://www.mdpi.com/1999-4923/14/2/411drug delivery into the braintransendothelium based on receptor-mediated transcytosisimmunotherapyAlzheimer’s diseaseanti-tau and anti-receptor bispecific monoclonal antibodiesAlzheimer’s disease-relevant tau species |
| spellingShingle | Toshihiko Tashima Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis Pharmaceutics drug delivery into the brain transendothelium based on receptor-mediated transcytosis immunotherapy Alzheimer’s disease anti-tau and anti-receptor bispecific monoclonal antibodies Alzheimer’s disease-relevant tau species |
| title | Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis |
| title_full | Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis |
| title_fullStr | Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis |
| title_full_unstemmed | Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis |
| title_short | Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis |
| title_sort | delivery of intravenously administered antibodies targeting alzheimer s disease relevant tau species into the brain based on receptor mediated transcytosis |
| topic | drug delivery into the brain transendothelium based on receptor-mediated transcytosis immunotherapy Alzheimer’s disease anti-tau and anti-receptor bispecific monoclonal antibodies Alzheimer’s disease-relevant tau species |
| url | https://www.mdpi.com/1999-4923/14/2/411 |
| work_keys_str_mv | AT toshihikotashima deliveryofintravenouslyadministeredantibodiestargetingalzheimersdiseaserelevanttauspeciesintothebrainbasedonreceptormediatedtranscytosis |