TY - JOUR
T1 - Statins and their potential targets in multiple sclerosis therapy
AU - Stüve, Olaf
AU - Prod'homme, Thomas
AU - Slavin, Anthony
AU - Youssef, Sawsan
AU - Dunn, Shannon
AU - Steinman, Lawrence
AU - Zamvil, Scott S.
N1 - Funding Information:
Support for this study was provided to SSZ by the Alexander M and June L Maisin Foundation (grant no. 98-416), the National Institutes of Health (grant no. K02 NS02207), the National Multiple Sclerosis Society (NMSS) (RG 3206-A-3), and the Nancy Davis Foundation. SSZ is a 2002 recipient of a research grant from the Wadsworth Foundation. OS is supported by an advanced fellowship from the NMSS and is a Boehringer-Ingelheim Fonds Scholar.
PY - 2003/10
Y1 - 2003/10
N2 - Multiple sclerosis (MS) is a CNS-demyelinating disease characterised by relapsing and chronic neurological impairment. While traditionally CNS autoantigen-specific CD4+ T cells have been considered the culprits in the initial phase of the disease, recent observations have altered this concept. It is now recognised that other T lymphocyte subclasses can initiate CNS demyelination. In addition, other cell types and molecules may play an important role in MS pathogenesis. There is overwhelming evidence that MS is a dynamic process, in which recurrent episodes of blood-brain barrier disruption and CNS inflammation play a crucial role in early disease stages, leading eventually to the largely irreversible changes of demyelination, gliosis and axonal degeneration. These observations may have important therapeutic implications. Within the last ten years, several medications have been approved for MS treatment. These agents, all of which are given parenterally, are only partially effective and are often associated with adverse effects and potential toxicities. The number and different types of medications used for MS are likely to increase in the near future, as several novel therapies are currently tested in clinical trials. 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, 'statins', are cholesterol-lowering drugs that are given orally, are safe and have biological effects independent of their cholesterol-reducing properties. Recent reports have shown that statins have anti-inflammatory and neuroprotective properties that may be beneficial in the treatment of MS. This article will outline experimental evidence that suggests potential clinical benefits of statins for MS patients.
AB - Multiple sclerosis (MS) is a CNS-demyelinating disease characterised by relapsing and chronic neurological impairment. While traditionally CNS autoantigen-specific CD4+ T cells have been considered the culprits in the initial phase of the disease, recent observations have altered this concept. It is now recognised that other T lymphocyte subclasses can initiate CNS demyelination. In addition, other cell types and molecules may play an important role in MS pathogenesis. There is overwhelming evidence that MS is a dynamic process, in which recurrent episodes of blood-brain barrier disruption and CNS inflammation play a crucial role in early disease stages, leading eventually to the largely irreversible changes of demyelination, gliosis and axonal degeneration. These observations may have important therapeutic implications. Within the last ten years, several medications have been approved for MS treatment. These agents, all of which are given parenterally, are only partially effective and are often associated with adverse effects and potential toxicities. The number and different types of medications used for MS are likely to increase in the near future, as several novel therapies are currently tested in clinical trials. 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, 'statins', are cholesterol-lowering drugs that are given orally, are safe and have biological effects independent of their cholesterol-reducing properties. Recent reports have shown that statins have anti-inflammatory and neuroprotective properties that may be beneficial in the treatment of MS. This article will outline experimental evidence that suggests potential clinical benefits of statins for MS patients.
KW - 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors
KW - Experimental autoimmune encephalomyelitis (EAE)
KW - Inflammation
KW - Multiple sclerosis (MS)
KW - Statins
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U2 - 10.1517/14728222.7.5.613
DO - 10.1517/14728222.7.5.613
M3 - Review article
C2 - 14498824
AN - SCOPUS:10744228682
SN - 1472-8222
VL - 7
SP - 613
EP - 622
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 5
ER -