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Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA
Pizzo ME, Plowey ED, Khoury N, Kwan W, Abettan J, DeVos SL, Discenza CB, Earr T et al.. Science (New York, N.Y.), 2025-08-07
Topic: Disease mechanisms in lab and animal studies
Amyloid-related imaging abnormalities (ARIA), side effects of anti-amyloid drugs seen in magnetic resonance imaging of the brain, are a major safety concern in patients with Alzheimer's disease. We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-β protein (anti-Aβ) using asymmetrical Fc mutations (ATV cisLALA ) that mitigates TfR-related liabilities and retains effector function when bound to Aβ. Administration of ATV cisLALA :Aβ in mice exhibited broad brain distribution and enhanced parenchymal plaque target engagement. This biodistribution reduced ARIA-like lesions and vascular inflammation. Taken together, ATV cisLALA has the potential to improve the next generation of Aβ immunotherapy through enhanced biodistribution mediated by transport across the blood-brain barrier.
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APA 7th
Pizzo, M. E., Plowey, E. D., Khoury, N., Kwan, W., Abettan, J., DeVos, S. L., et al. (2025). Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA. Science (New York, N.Y.). https://doi.org/10.1126/science.ads3204
Vancouver
Pizzo ME, Plowey ED, Khoury N, Kwan W, Abettan J, DeVos SL, et al. Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA. Science (New York, N.Y.). 2025. doi:10.1126/science.ads3204. PMID: 40773560.
BibTeX
@article{pizzo2025-40773560,
author = {Pizzo, M. E. and Plowey, E. D. and Khoury, N. and Kwan, W. and Abettan, J. and DeVos, S. L. and Discenza, C. B. and Earr, T. and others},
title = {{Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA}},
journal = {Science (New York, N.Y.)},
year = {2025},
doi = {10.1126/science.ads3204},
pmid = {40773560},
url = {https://doi.org/10.1126/science.ads3204}
}
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Key findings
- Taken together, ATV cisLALA has the potential to improve the next generation of Aβ immunotherapy through enhanced biodistribution mediated by transport across the blood-brain barrier.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40773560) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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