The Blood-Brain Barrier in Cortical Multiple Sclerosis Lesions.

CombiRX: The NIH makes a landmark study possible

Is A + B better than either alone?
MS researchers have also been asking this question. After preliminary pilot trials showed that taking Avonex plus Copaxone is safe, the National Institutes of Health (NIH) began a multi-million dollar trial last year to get solid answers about effectiveness.

Head to head and hand in hand
The CombiRX trial is taking place in more than 70 centers across North America . It's designed to involve 1,000 people with newly diagnosed relapsing MS. They will be followed for three years, to see if their responses hold up over time. The trial is "randomized" (meaning people are selected by chance to be in one of three groups) and "double-blind" (no one knows who is in which group), but it is not "placebo-controlled." Instead of giving some people an inactive placebo only, all volunteers receive at least one FDA-approved MS treatment. They all inject themselves every day (as is standard for Copaxone) and once a week (standard for Avonex). But for half of them, some of the shots are blanks.

From the Departments of Molecular Cell Biology and Immunology (JVH, HEV) and Pathology (BPB, PVV, LB), VU Medical Center Amsterdam, The Netherlands; and the National MS Competence Centre, Department of Neurology (LB), Haukeland University Hospital, University of Bergen, Norway.

The blood-brain barrier (BBB) is composed mainly of specialized endothelial cells characterized by the presence of intercellular tight junctions. Additionally, perivascular cells, astrocytes, and surrounding basement membranes determine BBB integrity. BBB disruption is an early phenomenon in the formation of new white matter multiple sclerosis (MS) lesions; however, knowledge of the extent of BBB changes in gray matter MS lesions is lacking. Here, we studied several markers for BBB integrity in well-characterized brain tissue of patients with MS. Plasma protein leakage was enhanced in white matter lesions compared with that in normal-appearing white matter, whereas plasma protein leakage was absent in gray matter lesions. White matter lesions showed irregular basement membranes and parenchymal depositions of collagen type IV, whereas purely gray matter lesions lacked basement membrane alterations. Similarly, we observed no evidence for astrogliosis and tight junction changes in cortical MS lesions. Although BBB dysfunction is a common feature of white matter MS lesions, cortical MS lesions lack markers for BBB disruption or astrogliosis. Our data may indicate that BBB breakdown is not a critical event in the formation of gray matter MS lesions.

PMID: 17413323 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17413323&itool=pubmed_DocSum