Neurology 2003;60:1234-1240
© 2003 American Academy of Neurology
Special Article
Neuroprotective agents for clinical trials in Parkinsons disease
A systematic assessment
B.M. Ravina, MD,
S.C. Fagan, PharmD,
R.G. Hart, MD,
C.A. Hovinga, PharmD,
D.D. Murphy, PhD,
T.M. Dawson, MD PhD and
J.R. Marler, MD
From the National Institute of Neurological Disorders and Stroke (Drs. Ravina, Hart, Murphy, and Marler) National Institutes of Health, Rockville, MD; Department of Pharmacology (Dr. Fagan), Medical College of Georgia, Augusta; Departments of Pharmacy and Neurology (Dr. Hovinga), Cleveland Clinic Foundation, OH; and Johns Hopkins University School of Medicine (Dr. Dawson), Baltimore, MD.
Address correspondence to Dr. Bernard M. Ravina, NINDS, Neuroscience Center, Rm 2225, 6001 Executive Blvd, Rockville, MD 20892-9257; e-mail: RavinaB{at}ninds.nih.gov
Background: Current therapies for PD ameliorate symptoms in the early phases of disease but become less effective over time, as the underlying disease progresses. Therapies that slow the progression of PD are needed. However, there have been relatively few clinical trials aimed at demonstrating neuroprotection. The authors sought to identify potential neuroprotective agents for testing in clinical trials.
Methods: First a broad array of compounds were identified by working with clinicians and researchers in academics and industry. Specific criteria were drafted for drug evaluation, including scientific rationale, bloodbrain barrier penetration, safety and tolerability, and evidence of efficacy in animal models or humans. Agents were prioritized based on these criteria.
Results: The authors identified 59 potential neuroprotective compounds, proposed by 42 clinicians and scientists from 13 countries. After systematic reviews using the specified criteria they found 12 compounds to be attractive candidates for further clinical trials in PD.
Conclusions: Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in PD.
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|
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322(3):
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|
 |
|

|
 |

|
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64(7):
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[Full Text]
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|
 |
|

|
 |

|
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4(2):
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|
 |
|

|
 |

|
 |
 
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38(2):
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|
 |
|

|
 |

|
 |
 
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67(7):
1262 - 1264.
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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67(7 Suppl 2):
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|
 |
|

|
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|
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67(1):
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|
 |
|

|
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|
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|
 |
|

|
 |

|
 |
 
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66(10_suppl_4):
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|
 |
|

|
 |

|
 |
 
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66(10_suppl_4):
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|
 |
|

|
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|
 |
 
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May 15, 2006;
63(10):
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|
 |
|

|
 |

|
 |
 
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66(5):
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|
 |
|

|
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66(5):
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|
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|
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January 11, 2006;
26(2):
535 - 541.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
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|
 |
 
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|
 |
|

|
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|
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|
 |
|

|
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|
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|
 |
|

|
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|
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|
 |
|

|
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|
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62(1):
158 - 159.
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[PDF]
|
 |
|

|
 |

|
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December 1, 2003;
60(12):
1680 - 1684.
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Neurology,
August 12, 2003;
61(3):
286 - 287.
[Full Text]
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|
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|
Correspondence:
Read all Correspondence
- Neuroprotective agents for clinical trials in Parkinson’s disease: A systematic assessment
- F Tison, et al.
- Neurology Online, 1 Jul 2003
[Full text]
- Reply to Letter to the Editor
- Bernard Ravina, et al.
- Neurology Online, 1 Jul 2003
[Full text]
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