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Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases
Wootla B, Watzlawik JO, Warrington AE, Wittenberg NJ, Denic A, Xu X, Jordan LR, Papke LM et al.. JAMA neurology, 2015-11-01
Topic: Brain proteins, microglia and lab models
Importance Modulating the immune system does not reverse long-term disability in neurologic disorders. Better neuroregenerative and neuroprotective treatment strategies are needed for neuroinflammatory and neurodegenerative diseases. Objective To review the role of monoclonal, naturally occurring antibodies (NAbs) as novel therapeutic molecules for treatment of neurologic disorders. Evidence review Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized clinical trials, and basic science reports, were identified in a PubMed search for articles about NAbs and neurologic disorders that were published from January 1, 1964, through June 30, 2015. We concentrated our review on multiple sclerosis, Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. Findings Many insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system. Central nervous system injury often results in a pervasive inhibitory microenvironment that hinders regeneration. A common targeted drug development strategy is to identify molecules with high potency in animal models. Many approaches often fail in the clinical setting owing to a lack of efficacy in human diseases (eg, less than the response demonstrated in animal models) or a high incidence of toxic effects. An alternative approach is to identify NAbs in humans because these therapeutic molecules have potential physiologic function without toxic effects. NAbs of the IgG, IgA, or IgM isotype contain germline or close to germline sequences and are reactive to self-components, altered self-components, or foreign antigens. Our investigative group developed recombinant, autoreactive, natural human IgM antibodies directed against oligodendrocytes or neurons with therapeutic potential for central nervous system repair. One such molecule, recombinant HIgM22, directed against myelin and oligodendrocytes completed a successful phase 1 clinical trial without toxic effects with the goal of promoting remyelination in multiple sclerosis. Conclusions and relevance Animal studies demonstrate that certain monoclonal NAbs are beneficial as therapeutic agents for neurologic diseases. This class of antibodies represents a unique source from which to develop a new class of disease-modifying therapies.
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APA 7th
Wootla, B., Watzlawik, J. O., Warrington, A. E., Wittenberg, N. J., Denic, A., Xu, X., et al. (2015). Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases. JAMA neurology. https://doi.org/10.1001/jamaneurol.2015.2188
Vancouver
Wootla B, Watzlawik JO, Warrington AE, Wittenberg NJ, Denic A, Xu X, et al. Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases. JAMA neurology. 2015. doi:10.1001/jamaneurol.2015.2188. PMID: 26389734.
BibTeX
@article{wootla2015-26389734,
author = {Wootla, B. and Watzlawik, J. O. and Warrington, A. E. and Wittenberg, N. J. and Denic, A. and Xu, X. and Jordan, L. R. and Papke, L. M. and others},
title = {{Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases}},
journal = {JAMA neurology},
year = {2015},
doi = {10.1001/jamaneurol.2015.2188},
pmid = {26389734},
url = {https://doi.org/10.1001/jamaneurol.2015.2188}
}
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Key findings
- Findings Many insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system.
- Central nervous system injury often results in a pervasive inhibitory microenvironment that hinders regeneration.
- Many approaches often fail in the clinical setting owing to a lack of efficacy in human diseases (eg, less than the response demonstrated in animal models) or a high incidence of toxic effects.
Why it matters
This is a review of naturally occurring antibodies as possible treatments for several neurologic diseases, including Alzheimer's disease, not a test of a treatment in patients. It notes that many approaches that work in animal models fail in humans due to lack of efficacy or toxic effects, so no treatment benefit is established here.
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Study details
- Study designclinical trial
- Evidence strengthHigh
How this study scored 41/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 17 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Moses Rodriguez: h-index 93 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26389734) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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