Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Published online before print September 19, 2007, doi:10.1212/01.wnl.0000277648.63931.c0)
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
01.wnl.0000277648.63931.c0v1
69/15/1480    most recent
Right arrow Correspondence:
Submit a response
Right arrow Correspondence:
View responses
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Received ,
Accepted ,

Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease

The Parkinson Study Group PRECEPT Investigators

ABSTRACT

Background: CEP-1347 inhibits mixed lineage kinases that activate apoptotic pathways implicated in the pathogenesis of Parkinson disease (PD). CEP-1347 enhances neuronal survival in a variety of nonclinical models and was found to be safe and well tolerated during 4 weeks in PD patients. We conducted the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) to assess its disease-modifying potential in early PD.

Methods: Consenting PD patients not yet requiring dopaminergic therapy (na806) were randomized equally to CEP-1347 in dosages of 10 mg BID, 25 mg BID, or 50 mg BID, or matching placebo, and were evaluated blindly and prospectively. The primary clinical end point was time to the development of disability requiring dopaminergic therapy. Secondary end points included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) and {beta}-CIT SPECT imaging of striatal dopamine transporters.

Results: The study was concluded early, after an average of 21.4 months of follow-up, when a planned interim analysis demonstrated that it would be futile to continue experimental treatment. At that time, 108 of 191 subjects randomized to placebo (57%) had reached the primary end point of disability requiring dopaminergic therapy compared with active CEP-1347: 133 of 205 (65%) on 10 mg BID, 126 of 212 (59%) on 25 mg BID, and 127 of 198 (64%) on 50 mg BID. Changes in UPDRS scores and {beta}-CIT imaging showed similar patterns.

Conclusions: In contrast to research in animal models that predicted favorable disease-modifying outcomes, we found CEP-1347 to be an ineffective treatment in early Parkinson disease.




This article has been cited by other articles:


Home page
 NeurologyHome page
E. Y. Uc, M. P. McDermott, K. S. Marder, S. W. Anderson, I. Litvan, P. G. Como, P. Auinger, K. L. Chou, J. C. Growdon, and On behalf of the Parkinson Study Group DATATOP Inv
Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort
Neurology, November 3, 2009; 73(18): 1469 - 1477.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
A. Ascherio, P. A. LeWitt, K. Xu, S. Eberly, A. Watts, W. R. Matson, C. Marras, K. Kieburtz, A. Rudolph, M. B. Bogdanov, et al.
Urate as a Predictor of the Rate of Clinical Decline in Parkinson Disease
Arch Neurol, October 12, 2009; (2009) 2009.247.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
C. W. Olanow, M. B. Stern, and K. Sethi
The scientific and clinical basis for the treatment of Parkinson disease (2009)
Neurology, May 26, 2009; 72(21_Supplement_4): S1 - S136.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. Marek and D. Jennings
Can we image premotor Parkinson disease?
Neurology, February 17, 2009; 72(7_Supplement_2): S21 - S26.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. E. Lang
When and how should treatment be started in Parkinson disease?
Neurology, February 17, 2009; 72(7_Supplement_2): S39 - S43.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Karunakaran, U. Saeed, M. Mishra, R. K. Valli, S. Datt Joshi, D. P. Meka, P. Seth, and V. Ravindranath
Selective Activation of p38 Mitogen-Activated Protein Kinase in Dopaminergic Neurons of Substantia Nigra Leads to Nuclear Translocation of p53 in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Mice
J. Neurosci., November 19, 2008; 28(47): 12500 - 12509.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
L. H. Wang, E. M. Johnson Jr, I. Shoulson, A. E. Lang, D. Bozyczko-Coyne, and On behalf of the Parkinson Study Group PRECEPT Inv
MIXED LINEAGE KINASE INHIBITOR CEP- 1347 FAILS TO DELAY DISABILITY IN EARLY PARKINSON DISEASE
Neurology, August 5, 2008; 71(6): 462 - 463.
[Full Text] [PDF]

Home page
 Arch NeurolHome page
M. A. Schwarzschild, S. R. Schwid, K. Marek, A. Watts, A. E. Lang, D. Oakes, I. Shoulson, A. Ascherio, and and the Parkinson Study Group PRECEPT Investigator
Serum Urate as a Predictor of Clinical and Radiographic Progression in Parkinson Disease
Arch Neurol, June 1, 2008; 65(6): 716 - 723.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. E. Ahlskog
I can't get no satisfaction: Still no neuroprotection for Parkinson disease
Neurology, October 9, 2007; 69(15): 1476 - 1477.
[Full Text] [PDF]

Correspondence:

Read all Correspondence

Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease
Leo H. Wang, et al.
Neurology Online, 24 Jan 2008 [Full text]
Reply from the authors
Ira Shoulson, et al.
Neurology Online, 24 Jan 2008 [Full text]

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by AAN Enterprises, Inc.