Journal
NEUROBIOLOGY OF DISEASE
Volume 56, Issue -, Pages 74-78Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2013.04.007
Keywords
Familial amyotrophic lateral sclerosis; Mutant superoxide dismutase type 1; Amyotrophic lateral sclerosis; ALS; Single chain fragments of variable region antibodies; scFvs; Motor neuron disease
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Funding
- National Institutes of Health [R21 NS066175]
- ALS Association [910]
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Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and similar to 25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. (c) 2013 Elsevier Inc. All rights reserved.
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