*MS Article-Tysabri*

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Hi

I only know what is written below I'm afraid. Adam:

Natalizumab Alters T Cell Ratio in MS Patients

(MS) alters the ratio of CD4+ to CD8+ T-cells in cerebrospinal fluid

(CSF), researchers have shown.

This may account for the development in some patients of progressive

multifocal leukoencephalopathy (PML), a demyelinating disorder of the

CNS caused by JC virus infection.

In the October issue of Neurology, Dr. Olaf Stuve of the VA North

Texas Health Care System, Dallas and colleagues note that natalizumab

(Tysabri) was voluntarily withdrawn from the market and its use was

stopped in clinical trials after two patients with MS and one with

Crohn's disease developed PML. Subsequently, Tysabri has been made

available again.

Natalizumab is a monoclonal antibody against the adhesion molecule,

very late activation antigen 4, which is an alpha-4-beta-1 integrin.

The team examined CSF and peripheral blood specimens from MS patients

who had undergone natalizumab therapy and found that CSF levels of

CD4+ to CD8+ were similar to those seen in HIV patients. Ratios

normalized within 6 months of cessation of natalizumab therapy.

The ratios in peripheral blood progressively decreased with the number

of natalizumab doses but remained within normal levels.

The researchers suggest that lower expression of unbound alpha4

integrin on CD4+ T cells may be a mechanism underlying the altered

T-cell ratios.

" Although the mechanism remains undefined at present, the implications

for immune control of CNS infections are potentially important, " the

researchers say, " and suggest that prolonged, uninterrupted

natalizumab therapy may eventually alter systemic immune responses. "

In an accompanying editorial, Drs. Henry F. McFarland and

sen of the National Institutes of Health, Bethesda, land note

that " careful biological monitoring " will be required as patients

return to treatment with natalizumab.

The results, they conclude, " have implications for not only

natalizumab but also other therapies that have similar mechanisms. "

Arch Neurol 2006;63:1383-1387