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Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials
Nimmo JT, Kelly L, Verma A, Carare RO, Nicoll JAR, Dodart JC.. Frontiers in neuroscience, 2021-09-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease and Lewy body diseases are the most common causes of neurodegeneration and dementia. Amyloid-beta (Aβ) and alpha-synuclein (αSyn) are two key proteins involved in the pathogenesis of these neurodegenerative diseases. Immunotherapy aims to reduce the harmful effects of protein accumulation by neutralising toxic species and facilitating their removal. The results of the first immunisation trial against Aβ led to a small percentage of meningoencephalitis cases which revolutionised vaccine design, causing a shift in the field of immunotherapy from active to passive immunisation. While the vast majority of immunotherapies have been developed for Aβ and tested in Alzheimer's disease, the field has progressed to targeting other proteins including αSyn. Despite showing some remarkable results in animal models, immunotherapies have largely failed final stages of clinical trials to date, with the exception of Aducanumab recently licenced in the US by the FDA. Neuropathological findings translate quite effectively from animal models to human trials, however, cognitive and functional outcome measures do not. The apparent lack of translation of experimental studies to clinical trials suggests that we are not obtaining a full representation of the effects of immunotherapies from animal studies. Here we provide a background understanding to the key concepts and challenges involved in therapeutic design. This review further provides a comprehensive comparison between experimental and clinical studies in Aβ and αSyn immunotherapy and aims to determine the possible reasons for the disconnection in their outcomes.
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APA 7th
Nimmo, J. T., Kelly, L., Verma, A., Carare, R. O., Nicoll, J. A. R., & Dodart, J. C. (2021). Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials. Frontiers in neuroscience. https://doi.org/10.3389/fnins.2021.733857
Vancouver
Nimmo JT, Kelly L, Verma A, Carare RO, Nicoll JAR, Dodart JC. Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials. Frontiers in neuroscience. 2021. doi:10.3389/fnins.2021.733857. PMID: 34539340.
BibTeX
@article{nimmo2021-34539340,
author = {Nimmo, J. T. and Kelly, L. and Verma, A. and Carare, R. O. and Nicoll, J. A. R. and Dodart, J. C.},
title = {{Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials}},
journal = {Frontiers in neuroscience},
year = {2021},
doi = {10.3389/fnins.2021.733857},
pmid = {34539340},
url = {https://doi.org/10.3389/fnins.2021.733857}
}
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Key findings
- The results of the first immunisation trial against Aβ led to a small percentage of meningoencephalitis cases which revolutionised vaccine design, causing a shift in the field of immunotherapy from active to passive immunisation.
- Despite showing some remarkable results in animal models, immunotherapies have largely failed final stages of clinical trials to date, with the exception of Aducanumab recently licenced in the US by the FDA.
- The apparent lack of translation of experimental studies to clinical trials suggests that we are not obtaining a full representation of the effects of immunotherapies from animal studies.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in neuroscience) |
| 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 | 3 / 5 | 2021 — within 6 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 34539340) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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