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Title: Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing-remitting Multiple Sclerosis (ASIIMS) trial
Authors: Gonsette, Richard E.
Sindic, Christian
D'hooghe, Marie B.
De Deyn, Peter-Paul
Michotte, Alex
Seeldrayers, Pierrette
Guillaume, Daniel
Issue Date: 2010
Source: MULTIPLE SCLEROSIS, 16 (4). p. 455-462
Abstract: Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon beta) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon beta alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon beta for at least 6 months were randomized to interferon beta+ inosine or interferon beta+ placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (<= 10 mg/dl). The primary end points were percentage of patients with progression of disability and time to sustained progression (Kaplan-Meier analysis). The combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone. We conclude that endogenous neuroprotective mechanisms recently identified in multiple sclerosis are complex and uric acid does not reflect the entire story.
Notes: [Gonsette, Richard E.] Natl Ctr Multiple Sclerosis, B-1820 Melsbroek, Belgium. [Sindic, Christian] Clin Univ St Luc, B-1200 Brussels, Belgium. [D'hooghe, Marie B.] Natl Multiple Sclerose Ctr, B-1820 Melsbroek, Belgium. [De Deyn, Peter-Paul] Algemeen Ziekenhuis Midellheim, B-2020 Antwerp, Belgium. [Medaer, Robert] Univ Limburg, Ctr Biomed, Onderzoekinst, B-3590 Diepenbeek, Belgium. [Michotte, Alex] Univ Ziekenhuis, Brussels, Belgium. [Seeldrayers, Pierrette] CHU, B-6000 Charleroi, Belgium. [Guillaume, Daniel] Ctr Neurol & Readaptat Fonct, B-4557 Fraiture, Belgium.
Keywords: endogenous neuroprotection; inosine; multiple sclerosis; neurodegeneration; uric acid;endogenous neuroprotection; inosine; multiple sclerosis; neurodegeneration; uric acid
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ISSN: 1352-4585
e-ISSN: 1477-0970
DOI: 10.1177/1352458509360547
ISI #: 000276530000010
Category: A1
Type: Journal Contribution
Validations: ecoom 2011
Appears in Collections:Research publications

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