Galea, Ian, Copple, Ian M 
ORCID: 0000-0003-4101-1913, Howat, David W and Franklin, Stephen
(2019)
SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis.
MULTIPLE SCLEROSIS AND RELATED DISORDERS, 30.
pp. 257-261.
Abstract
<h4>Background</h4>Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a master transcriptional regulator of the protective cellular response to oxidative stress. Sulforaphane is a Nrf2 activator but is unstable at ambient temperature. SFX-01 is a novel composition comprised of synthetic sulforaphane stabilised within the pocket of an α-cyclodextrin complex. Here we tested the efficacy of SFX-01 in murine relapsing experimental autoimmune encephalomyelitis (EAE), a model of relapsing-remitting MS (RRMS).<h4>Methods</h4>Relapsing EAE was induced in female SJL mice using immunization against PLP<sub>139-151</sub>. In the therapeutic experiment, the aim was to model initiation of treatment after diagnosis in RRMS, so treatment was started at day 19, one day prior to the expected relapse onset. In the prophylactic experiment, mice were treated from the time of immunization and followed for three weeks.<h4>Results</h4>SFX-01 reduced residual disability in both experiments. Most of this effect was mediated by a decrease in maximum severity of relapses and improved recovery during follow-up. Histological examination of the spinal cord was consistent with the clinical findings, with improvement in demyelination and the number of apoptotic cells, but not inflammatory cell infiltration, compared to the vehicle group.<h4>Conclusions</h4>SFX-01 is efficacious in EAE. In first-in-man and phase II clinical trials for other indications, SFX-01 was found to be well-tolerated. A trial comparing BG-12 and SFX-01 would address whether SFX-01 can offer RRMS patients a better option with respect to efficacy and tolerability.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Animals, Mice, Encephalomyelitis, Autoimmune, Experimental, Disease Models, Animal, Isothiocyanates, Sulfoxides, Myelin Proteolipid Protein, Peptide Fragments, Anticarcinogenic Agents, Freund's Adjuvant, Disability Evaluation, Treatment Outcome, Dose-Response Relationship, Drug, Time Factors, Female, Kaplan-Meier Estimate |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Mar 2019 13:58 |
| Last Modified: | 19 Jan 2023 00:57 |
| DOI: | 10.1016/j.msard.2019.02.027 |
| Open Access URL: | https://www.sciencedirect.com/science/article/pii/... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3034282 |
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