Rasagiline alone and in combination with riluzole prolongs survival in an ALS mouse model

被引:93
作者
Waibel, S
Reuter, A
Malessa, S
Blaugrund, E
Ludolph, AC
机构
[1] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany
[2] Teva Pharmaceut Ltd, Dev Unit, Netanya, Israel
关键词
amyotrophic lateral sclerosis; motor neuron disease; rasagiline; G93A animals; experimental therapeutics;
D O I
10.1007/s00415-004-0481-5
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Rasagiline is an antiapoptotic compound with neuroprotective potential. We examined its neuroprotective effect alone and in combination with the putative glutamate release blocker riluzole in the G93A model of familial amyotrophic lateral sclerosis (fALS). Endpoints of experimental treatment were survival and motor activity. The drug had a significant dose-dependent therapeutic effect on both preclinical and clinical motor function and survival of the animals. We also found that the combination of rasagiline with riluzole is safe and increases survival by about 20% in a dose-dependent manner. Therefore, we conclude that the combination of rasagiline and riluzole is a promising clinical combination for the improvement of current neuroprotective treatment strategies of ALS.
引用
收藏
页码:1080 / 1084
页数:5
相关论文
共 18 条
[1]  
Brooks BR, 2001, AMYOTROPH LATERAL SC, V2, P60
[2]   From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS [J].
Cleveland, DW ;
Rothstein, JD .
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (11) :806-819
[3]   The pharmacology and mechanism of action of riluzole [J].
Doble, A .
NEUROLOGY, 1996, 47 (06) :S233-S241
[4]   Rasagiline and its (S) enantiomer increase survival and prevent stroke in salt-loaded stroke-prone spontaneously hypertensive rats [J].
Eliash, S ;
Speiser, Z ;
Cohen, S .
JOURNAL OF NEURAL TRANSMISSION, 2001, 108 (8-9) :909-923
[5]   Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation [J].
Ferrante, RJ ;
Shinobu, LA ;
Schulz, JB ;
Matthews, RT ;
Thomas, CE ;
Kowall, NW ;
Gurney, ME ;
Beal, MF .
ANNALS OF NEUROLOGY, 1997, 42 (03) :326-334
[6]   MOTOR-NEURON DEGENERATION IN MICE THAT EXPRESS A HUMAN CU,ZN SUPEROXIDE-DISMUTASE MUTATION [J].
GURNEY, ME ;
PU, HF ;
CHIU, AY ;
DALCANTO, MC ;
POLCHOW, CY ;
ALEXANDER, DD ;
CALIENDO, J ;
HENTATI, A ;
KWON, YW ;
DENG, HX ;
CHEN, WJ ;
ZHAI, P ;
SUFIT, RL ;
SIDDIQUE, T .
SCIENCE, 1994, 264 (5166) :1772-1775
[7]   Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familiar amyotrophic lateral sclerosis [J].
Gurney, ME ;
Cutting, FB ;
Zhai, P ;
Doble, A ;
Taylor, CP ;
Andrus, PK ;
Hall, ED .
ANNALS OF NEUROLOGY, 1996, 39 (02) :147-157
[8]   Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse [J].
Huang, W ;
Chen, Y ;
Shohami, E ;
Weinstock, M .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 366 (2-3) :127-135
[9]  
Kong JM, 1998, J NEUROSCI, V18, P3241
[10]   Dose-ranging study of riluzole in amyotrophic lateral sclerosis [J].
Lacomblez, L ;
Bensimon, G ;
Leigh, PN ;
Guillet, P ;
Meininger, V .
LANCET, 1996, 347 (9013) :1425-1431