The Changing Times of Multiple Sclerosis Treatment

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Category: Multiple Sclerosis Published on Wednesday, 25 June 2008 Written by Yong Tsai, MD
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Multiple sclerosis (MS), an autoimmune disease in the central nerve system, is like the Civil War.  It occurs when our body's immune system turns our own lymphocytes, cells that protect us from infection and tumors, against our own brain and spinal cord.  Because inflammation can damage nerve tissue, eventually, damaged tissue turns into scar tissue (sclerosis), meaning "multiple sclerosis".

Classic symptoms of MS include numbness, visual disturbance, abnormal gait, imbalance, muscle weakness or spasm, urinary incontinence, vertigo, slurred speech or even pain.

Relapsing-remitting MS, the most common form, occurs about 25% of the time and is characterized by intermittent relapses with worsening of existing symptoms or the development of new symptoms.  Over the course of 10-15 years, about 50 % RRMS evolve into progressive MS, known for more frequent relapses, incomplete remission bouts, and general overall deterioration.

Previously treated with corticosteroids and immunosuppressants such as cyclophosphamide or azathioprine, MS remained unsatisfactorily controlled with frequent side effects.  During the past few years, beta interferons (naturally occurring proteins) such as Avonex, Rebif, Betaseron and Glatiramer acetate (a mixture of amino acids), have been used for treatment of relapsing-remitting MS.  Essentially, these disease-modifying therapies worked by adjusting our autoimmune and inflammatory process by decreasing the recurrence and intensity of relapses.  However, they still have side effects and unsatisfactory results for some patients with MS.

Last November, Natalizumab (Tysabri), a monoclonal antibody, targets and disables key molecules that play an important role in transporting lymphocytes to our central nervous system, which can cause nerve tissue damage, was approved by the FDA. Clinical trials have shown Tysabri, a monthly intravenous infusion, more effective than other disease-modifying therapies in reducing relapses and decreasing new brain lesions.  This is a breakthrough treatment for patients with relapsing-remitting MS.

However, the shocking news surfaced February 28th that Tysabri was suspended from commercial distribution based on reports of two serious adverse events that occurred in clinical trial patients treated with Tysabri in combination with Avonex.  These events involve one fatal, confirmed case and one suspected case of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal demyelinating disease.   There have been no apparent reports of PML in multiple sclerosis patients treated with monotherapy with either Tysabri or Avonex.   However, because of the possible risk of PML, which is currently being evaluated, Tysabri‚Äôs fate remains unclear at present.

Finding a drug that can properly intervene with our immune system is complicated and tricky.  The biggest challenge remains being able to suppress our immune system just enough to stop the autoimmune process, but not to over do it to prevent activating dormant infection or tumor.

Although recent headlines about Tysabri are a big setback, the future of MS treatment still looks bright.

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