Harbige, L. S., Hollifield, R. D., Pinto, E., Xiang, M., Leach, M. ORCID: 0000-0002-9859-1325 and Sharief, M. K. (2006) Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis. In: 7th Congress of the ISSFAL, International Society for the Study of Fatty Acids & Lipids (ISSFAL 2006), 23–28 July 2006, Cairns Convention Centre, Cairns, Queensland, Australia. (Unpublished)

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Abstract

Background: multiple sclerosis (MS) is a CNS-specific demyelinating disease with most patients demonstrating a relapse-remitting form of the disease, characterised by attacks (relapses) and periods of recovery (remission). Although the aetiology of MS remains unknown much evidence suggests the presence of autoimmune mechanisms in the disease pathogenesis. We have found cytokine dysregulation in peripheral blood mononuclear cells (PBMC) during the relapse-remitting phases of the disease i.e. raised TNFα and IL-1β and lack of regulatory TGFβ production. Furthermore these changes are associated with loss of ω-6 fatty acids particularly LA (18:2ω-6) and AA (20:4ω-6) during the relapse-remission phases of the disease in addition to other fatty acid metabolic changes. Aim: To determine the effects of a selected GLA(18:3ω-6)-rich oil (BGC20-884) at two doses (a low and a high dose) and a placebo control (PEGA) on the clinical course and PBMC cytokine and membrane fatty acid profiles of 36 patients with active MS in a randomized double-blind placebo controlled trial format over 18 months. Methods: Patients were diagnosed and assessed using international criteria for MS. Relapse rate and EDSS (Expanded Disability Status Scale) were assessed every three months and blood taken and the PBMC isolated for cytokine studies and membrane fatty acids. Results: High dose BGC20-884 treatment markedly and significantly reduced the relapse rate and disability progression (EDSS) compared with the placebo control and low dose BGC20-884 treatment. Indeed the high dose BGC20-884 treated group showed improvement in EDSS. PBMC cytokine changes were found to run parallel with the clinical findings with high dose BGC20-884 treatment showing no changes in TGFβ/TNFα ratio and TGFβ/IL-1β ratio whilst the placebo control and BGC20-884 low dose group showed significant decreases in the TGFβ/TNFα ratio and TGFβ/IL-1β ratio over time. Conclusion: High dose BGC20-884 markedly affected the clinical course of MS with parallel changes in the production of pro-inflammatory cytokines (TNFα,IL-1β) and anti-inflammatory (TGFβ) cytokines. Furthermore the EDSS improvement in the high dose group suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. This study supports the hypothesis of dysregulation of cytokines and fatty acid metabolism in MS and establishes some scientific principles for further evaluation of GLA supplementation in MS.

Item Type:	Conference or Conference Paper (Paper)
Additional Information:	[1] This paper (1400) was presented at the 7th Congress of the ISSFAL, International Society for the Study of Fatty Acids & Lipids, (ISSFAL 2006), incorporating the 6th International Congress on Essential Fatty Acids and Eicosanoids and PUFA in Maternal and Infant Health 2006 Annual Scientific Meetings held from 23-28 July 2006, at the Cairns Convention Centre, Cairns, Queensland, Australia. This paper was presented on 27 July 2006.
Uncontrolled Keywords:	fatty acids, pathogenesis, treatment, multiple sclerosis
Subjects:	Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology Q Science > QR Microbiology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > School of Science (SCI) Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Related URLs:	Organisation Organisation
Last Modified:	09 Oct 2021 04:46
URI:	http://gala.gre.ac.uk/id/eprint/3316

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