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Neuroprotection: The Future for the Treatment of Progressive Multiple Sclerosis?

Neuroprotection: The Future for the Treatment of Progressive Multiple Sclerosis?. Dennis Bourdette, MD VA MS Center of Excellence-West and Department of Neurology Oregon Health & Science University. CMSC, June 2004. MS is an Inflammatory Disease.

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Neuroprotection: The Future for the Treatment of Progressive Multiple Sclerosis?

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  1. Neuroprotection: The Future for the Treatment of Progressive Multiple Sclerosis? Dennis Bourdette, MD VA MS Center of Excellence-West and Department of Neurology Oregon Health & Science University CMSC, June 2004

  2. MS is an Inflammatory Disease Cartoon of cells in spinal cord (plasma, regulatory T cells, pathogenic T cells, antibodies) CMSC, June 2004

  3. Neuroprotection in MS • Current DMT are primarily anti-inflammatory • DMT are ineffective in treating progressive forms of MS • Progressive neurodegenerative axonopathy may underlie progressive disease • “Neuroprotective” therapies may be necessary to arrest progressive disease CMSC, June 2004

  4. The Pathogenesis of MS May Involve Both Inflammation and Neurodegeneration CMSC, June 2004

  5. MS and Axonal Loss Adams, A Colour Atlas of Multiple Sclerosis, 1989

  6. Cerebral Atrophy Occurs in MS Courtesy of Richard Rudick, MD

  7. MS and Acute Axonal Injury Trapp et al, N Engl J Med, 338:278, 1998

  8. How Can We Prevent Brain Atrophy?

  9. Strategies • Early highly effective anti-inflammatory therapy • Neuroprotective therapies to prevent oligodendrocyte and axonal injury • Promote remyelination • Provide missing “trophic factors” CMSC, June 2004

  10. Glutamate Receptor Blockade is Neuroprotective in EAE Pitt et al, Nature Medicine 6:67, 2000

  11. Glutamate Receptor Blockade is Neuroprotective in EAE Pitt et al, Nature Medicine 6:67, 2000

  12. Phenytoin protects Axons in EAE: Na+ Channel Blockade Lo et al, NeuroReport 13:1909, 2002

  13. FK506 Decreases Spinal Cord White Matter Damage Gold et al, J Neurosci Res, 2004

  14. FK506 Decreases Axonal Loss and Demyelination Saline FK506 Gold et al, J Neurosci Res, 2004

  15. Without FK506 With FK506 Neurons Neurons Neurite Neurite Courtesy of Dr. Bruce Gold

  16. MS and Remyelination Adams, A Colour Atlas of Multiple Sclerosis, 1989

  17. MS and Remyelination Adams, A Colour Atlas of Multiple Sclerosis, 1989

  18. Obstacles • It is uncertain how we should be studying neuroprotective therapies • MRI measurements • Slowing of clinical disability • Experience in other neurologic diseases with neuroprotective therapies is discouraging • Stroke • ALS • PD CMSC, June 2004

  19. Conclusions • We should continue to treat early and develop highly effective anti-inflammatory regimens • Neuroprotective and neuroregenerative therapies need to be tested in MS CMSC, June 2004

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