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Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools
Lichtlen P, Mohajeri MH.. Journal of neurochemistry, 2007-11-06
Topic: Amyloid, tau and blood-test diagnosis
High morbidity, enormous socioeconomic costs, and lack of specific treatments emphasize the importance of research on protective therapies against Alzheimer's disease. The efficacy of anti-amyloid immunization strategies has been demonstrated preclinically, prompting the design of clinical studies. However, the detailed mechanisms of action of therapeutic antibodies, especially their influence on the complex amyloid beta peptide (Abeta) metabolism and various Abeta-equilibria present both within and outside the CNS, are far from being clear. Furthermore, physiological Abeta metabolism is poorly understood and the analytical tools to characterize and quantify treatment effects on Abeta metabolism are suboptimal. Thus, the design of immunization strategies with optimized benefit-to-risk ratios for patients is subjected to significant obstacles. Indeed, an active immunization trial with Abeta was discontinued because of severe adverse effects. Anti-Abeta immunization protocols designed to attain high blood levels of antibodies bear the potential to induce brain inflammation and/or hemorrhage, thus directing the biomedical research towards development of more predictable therapies for minimizing the risk of adverse effects. The focus of this review is to summarize current knowledge of Abeta metabolism under physiological and antibody-based therapeutic conditions and to introduce a promising approach, namely the passive immunization using antibody fragments, which are characterized by entirely different pharmacokinetic and pharmacodynamic properties compared with conventional monoclonal antibodies.
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APA 7th
Lichtlen, P., & Mohajeri, M. H. (2008). Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools. Journal of neurochemistry. https://doi.org/10.1111/j.1471-4159.2007.05064.x
Vancouver
Lichtlen P, Mohajeri MH. Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools. Journal of neurochemistry. 2008. doi:10.1111/j.1471-4159.2007.05064.x. PMID: 17986215.
BibTeX
@article{lichtlen2008-17986215,
author = {Lichtlen, P. and Mohajeri, M. H.},
title = {{Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools}},
journal = {Journal of neurochemistry},
year = {2008},
doi = {10.1111/j.1471-4159.2007.05064.x},
pmid = {17986215},
url = {https://doi.org/10.1111/j.1471-4159.2007.05064.x}
}
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Key findings
- The efficacy of anti-amyloid immunization strategies has been demonstrated preclinically, prompting the design of clinical studies.
- Thus, the design of immunization strategies with optimized benefit-to-risk ratios for patients is subjected to significant obstacles.
- The focus of this review is to summarize current knowledge of Abeta metabolism under physiological and antibody-based therapeutic conditions and to introduce a promising approach, namely the passive immunization using antibody fragments, which are characterized by entirely different pharmacokinetic and pharmacodynamic properties compared with conventional monoclonal antibodies.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed 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 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurochemistry) |
| 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 | 1 / 5 | 2008 — within 20 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 17986215) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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