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SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis

SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis
SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis

Background: 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). Methods: Relapsing EAE was induced in female SJL mice using immunization against PLP 139-151 . 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. Results: 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. Conclusions: 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.

2211-0348
257-261
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Copple, Ian M.
aaf11608-4bbd-4556-b058-7347d5688137
Howat, David W.
88f9d2d2-df7a-415b-9fbe-aa8ac310a4a5
Franklin, Stephen
dd17231b-e945-4df8-8092-5e6e6a6a7daa
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Copple, Ian M.
aaf11608-4bbd-4556-b058-7347d5688137
Howat, David W.
88f9d2d2-df7a-415b-9fbe-aa8ac310a4a5
Franklin, Stephen
dd17231b-e945-4df8-8092-5e6e6a6a7daa

Galea, Ian, Copple, Ian M., Howat, David W. and Franklin, Stephen (2019) SFX-01 reduces residual disability after experimental autoimmune encephalomyelitis. Multiple Sclerosis and Related Disorders, 30, 257-261. (doi:10.1016/j.msard.2019.02.027).

Record type: Article

Abstract

Background: 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). Methods: Relapsing EAE was induced in female SJL mice using immunization against PLP 139-151 . 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. Results: 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. Conclusions: 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.

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Accepted/In Press date: 25 February 2019
e-pub ahead of print date: 26 February 2019
Published date: 1 May 2019

Identifiers

Local EPrints ID: 429001
URI: https://eprints.soton.ac.uk/id/eprint/429001
ISSN: 2211-0348
PURE UUID: 4d4dd9c5-240d-41d8-a68b-f68e4617ea76
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 18 Mar 2019 17:30
Last modified: 19 Jul 2019 10:14

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