Single chain variable fragment antibodies directed against SOD1 ameliorate disease in mutant SOD1 transgenic mice
Open accessAbstract
Mutations in Cu/Zn superoxide dismutase (SOD1) are the cause of ~20% of cases of familial ALS (FALS), which comprise ~10% of the overall total number of cases of ALS. Mutant (mt) SOD1 is thought to cause FALS through a gain and not loss in function, perhaps as a result of the mutant protein's misfolding and aggregation. Previously we used a phage display library to raise single chain variable fragment antibodies (scFvs) against SOD1, which were found to decrease aggregation of mtSOD1 and toxicity in vitro. In the present study, we show that two scFvs directed against SOD1 ameliorate disease in G93A mtSOD1 transgenic mice and also decrease motor neuron loss, microgliosis, astrocytosis, as well as SOD1 burden and aggregation. The results suggest that the use of antibodies or antibody mimetics directed against SOD1 may be a useful therapeutic direction in mtSOD1-induced FALS. Since studies suggest that wild type SOD1 may be misfolded similar to that seen with mtSOD1, this therapeutic direction may be effective in sporadic as well as FALS.
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Phage-specific raised single-chain variable fragment antibodies (scFvs) against SOD1G93A in mice reduced motor neuron loss, microgliosis, astrocytosis, and SOD1 burden and aggregation.
“Ghadge et al. (123) used phage-specific raised single-chain variable fragment antibodies (scFvs) against SOD1G93A in mice and found that these antibodies reduced motor neuron loss, microgliosis, astrocytosis, and SOD1 burden and aggregation.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [123]
Improvements were observed in the aggregation and in vitro toxicity of mutant SOD1.
“Improvements were observed in the aggregation and in vitro toxicity of mutant SOD1.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [123]
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- Authors
- Ghadge, G. D., Kay, B. K., Drigotas, C., & Roos, R. P.
- Affiliations
- University of Chicago Medical Center (US)
- University of Illinois Chicago (US)
- Corresponding author
- Roos, Raymond P.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 121
- Pages
- 131-137
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2889043080
- Cited by
- 28
- References
- 29
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 3 · 2022: 10 · 2021: 1 · 2020: 5 · 2019: 4
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- ALS Association
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- scFv, SOD1, familial ALS, protein aggregation, antibody therapy, motor neuron degeneration, microglial activation, astrocyte activation, phage display, gain-of-function toxicity
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Disease Models, Animal, Female, Gliosis, Male, Mice, Inbred C57BL, Mice, Transgenic, Motor Neurons, Spinal Cord, Superoxide Dismutase, Single-Chain Antibodies, Protein Aggregation, Pathological
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