Multiple Sclerosis: Duda P

Sørensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J, Polman C, Pozzilli C, Ross C, Anonymous00318. · Danish Multiple Sclerosis Research Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Eur J Neurol. · Pubmed #16241970 No free full text.

Abstract: Therapy-induced binding and neutralizing antibodies is a major problem in interferon (IFN)-beta treatment of multiple sclerosis. The objective of this study was to provide guidelines outlining the methods and clinical use of the measurements of binding and neutralizing antibodies. Systematic search of the Medline database for available publications on binding and neutralizing antibodies was undertaken. Appropriate publications were reviewed by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. Measurements of binding antibodies are recommended for IFN-beta antibody screening before performing a neutralizing antibody (NAB) assay (Level A recommendation). Measurement of NABs should be performed in specialized laboratories with a validated cytopathic effect assay or MxA production assay using serial dilution of the test sera. The NAB titre should be calculated using the Kawade formula (Level A recommendation). Tests for the presence of NABs should be performed in all patients at 12 and 24 months of therapy (Level A recommendation). In patients who remain NAB-negative during this period measurements of NABs can be discontinued (Level B recommendation). In patient with NABs, measurements should be repeated, and therapy with IFN-beta should be discontinued in patients with high titres of NABs sustained at repeated measurements with 3- to 6-month intervals (Level A recommendation).

Kappos L, Duda P. · No affiliation provided · Brain. · Pubmed #12390965 links to  free full text

This publication has no abstract.

Scagnolari C, Duda P, Bagnato F, De Vito G, Alberelli A, Lavolpe V, Girardi E, Durastanti V, Trojano M, Kappos L, Antonelli G. · Dept. of Experimental Medicine - Virology Section, La Sapienza University, Rome, Italy. · J Neurol. · Pubmed #17420930 No free full text.

Abstract: To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs. The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively). Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB-patients and between patients with high (> 200 t(1/10)) and low ( pound 200 t(1/10)) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner.

Kappos L, Polman C, Thompson AJ, Duda P, Clanet M, Comi G, Hartung HP, Montalban X. · Outpatient Clinic Neurology-Neurosurgery, University Hospitals, Basel, Switzerland. · Mult Scler. · Pubmed #14664478 No free full text.

Abstract: Quality standards for clinical studies in the field of multiple sclerosis (MS) have improved significantly, to the great benefit of patients. This development has been accompanied by soaring costs and ever increasing complexity, with industry-independent trials having become virtually impossible. We propose establishing a European network that would include expertise in all the relevant aspects of MS treatment trials. In a stepwise approach, all interested active centres across Europe should be recruited into the network, based on agreement upon common scientific standards and quality requirements. Three main goals are discussed: to facilitate identification of potentially useful agents for MS treatment; to establish protocols for the interaction between investigators and industry; and to identify common standards and a core set of data to allow for comparisons of MS trials. Collaboration with existing international organizations and institutions, especially the Sylvia Lawry Centre for MS Research, as well as with similar initiatives in North America and other parts of the world is envisaged.