Future research directions in multiple sclerosis therapies

Benjamin M. Greenberg, Peter A. Calabresi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The success of presently available injectable immunomodulatory therapies in treating multiple sclerosis has led to heightened interest in finding even more efficacious and better tolerated therapies. Several oral agents have shown efficacy in phase-II clinical trials and are now entering phase-III pivotal trials. In addition, monoclonal antibodies targeting surface receptors on various cells of the peripheral immune system have also shown efficacy in early studies and will soon be entering phase III. All of these approaches target immune molecules that are not specific for multiple sclerosis (MS) and carry inherent risk of infection and systemic side effects. Novel immunotherapies in preclinical or phases I to IIa testing are attempting to more selectively target pathogenic effector cells and thereby block abnormal immune cell activation without compromising normal healthy immune responses. The induction of tolerance to self-proteins continues to be a goal of MS immunotherapy, but as yet has not been accomplished outside of the laboratory. There is increasing awareness of the need to understand and modulate nonclassical immune targets as well as central nervous system degenerative processes. The roles of vitamins, antimicrobials, and hormones continue to be studied. The mechanisms of neurodegeneration in MS are likely multifactorial and include direct damage by T cells and humoral immunity as well as oxidative stress, glutamate-mediated excitotoxicity, and neuronal and oligodendrocyte apoptosis. Neuroprotective drugs that were once only considered for classical degenerative diseases, such as amyotrophic lateral sclerosis and Parkinson's disease, are now being considered in MS.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalSeminars in Neurology
Volume28
Issue number1
DOIs
StatePublished - Feb 2008

Fingerprint

Multiple Sclerosis
Immunotherapy
Therapeutics
Phase II Clinical Trials
Immunomodulation
Oligodendroglia
Amyotrophic Lateral Sclerosis
Neuroprotective Agents
Humoral Immunity
Vitamins
Parkinson Disease
Glutamic Acid
Immune System
Oxidative Stress
Central Nervous System
Monoclonal Antibodies
Direction compound
Hormones
Apoptosis
T-Lymphocytes

Keywords

  • Clinical trials
  • Immunosuppression
  • Monoclonal antibodies
  • Multiple sclerosis
  • Neuroprotection

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Future research directions in multiple sclerosis therapies. / Greenberg, Benjamin M.; Calabresi, Peter A.

In: Seminars in Neurology, Vol. 28, No. 1, 02.2008, p. 121-127.

Research output: Contribution to journalArticle

Greenberg, Benjamin M. ; Calabresi, Peter A. / Future research directions in multiple sclerosis therapies. In: Seminars in Neurology. 2008 ; Vol. 28, No. 1. pp. 121-127.
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