Autologous Stem cell Transplantation International Multiple Sclerosis

Multiple sclerosis (MS)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (brain and spinal cord), characterized by abnormal attacks against the protective sheath surrounding nerve fibres, called myelin; attacks are mediated by immune-competent cells, and MS is thought to be an autoimmune disease. The clinical course is very heterogeneous, and people with MS can expect one of four clinical courses of the disease; clinical manifestations are also heterogeneous and vary considerably between different patients within the same MS type, and over time. Later in the disease course, nerves, already damaged and uncovered by the enveloping myelin sheath, degenerate through unknown mechanisms leading to progressive worsening of the neurological condition with chronic disability.

Measurement of disease activity and disability

For a patient and their family, the most important measurement of disease activity is their ability to function in daily life. This is measured by a standardised system called: the Extended Disability Status Scale (EDSS) from 0 to 10. Low scores mean little disease disability.

The treating doctor is also interested in the amount of inflammation in the brain caused by the disease which does not always correlate directly with the general function of the patient.
This inflammation may be measured with Magnetic Resonance Imaging (MRI) combined with contrast medium, a non-invasive technique.

Currently available therapies

Currently available therapies exert some effect on the frequency and severity of exacerbations and the number of lesions as seen on MRI, although the effect on progression of disability remains unclear. Interferons and glatiramer acetate reduce the amount of relapses by about one third, but, with respect to disease progression, only IFN _ 1b has a modest beneficial effect on disability progression in secondary progressive (SP) MS. The role of conventional drugs that suppress the immune system (such as azathioprine or methotrexate) is not convincing. Recently, Natalizumab, a monoclonal antibody against integrin-_4, has proven efficacy in the treatment of MS, showing to reduce relapse rate and slowing the progression of disability

Natalizumab

Natalizumab is a monoclonal antibody against integrin-_4, and its mechanism of action is believed to involve the inhibition of immune cells from crossing blood vessel walls to reach various tissues, including the brain. In MS, natalizumab was shown to reduce relapses by 67% vs. a placebo. It slowed the progression of disability (as measured by EDSS) by 42%. While the drug was shown to be powerfully effective for preventing relapses of MS, just three months after his initial approvation for MS by the FDA, one fatal and one non-fatal case of progressive multifocal leukoencephalopathy (PML) were found in patients given natalizumab, so the drug was voluntarily withdrawn from the market. On June 5, 2006, after reviewing two years of safety and efficacy, FDA re-approved it for patients with relapsing forms of MS under certain conditions. In April 2006 the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), issued a positive opinion recommending marketing authorization for natalizumab as a treatment for relapsing-remitting multiple sclerosis.

Mitoxantrone

Only Mitoxantrone has a demonstrated effect on magnetic resonance imaging (MRI) activity and can slow down the progression of disability in secondary progressive MS. It is the only immunosuppressive drug approved for the treatment of worsening relapsing remitting MS, SP MS and progressive relapsing MS. However, it shows some cumulative cardiac toxicity and can be utilized during the lifetime for only a period or for a single cycle of therapy. Indeed, many patients continue to worsen in spite of treatment. Therefore, the search for more effective immunosuppressive therapies is needed.