Document Detail

Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic Acid in patients with amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  19935406     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 to 5 years. Neuronal cell death offers a potential target for therapeutic intervention. Ursodeoxycholic acid is a cytoprotective, endogenous bile acid that has been shown to be neuroprotective in experimental Huntington and Alzheimer diseases, retinal degeneration, and ischemic and hemorrhagic stroke. The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration. METHODS: Eighteen patients were randomly assigned to receive ursodeoxycholic acid at doses of 15, 30, and 50 mg/kg of body weight per day. Serum and cerebrospinal fluid were obtained for analysis after 4 weeks of treatment. Treatment-emergent clinical and laboratory events were monitored weekly. RESULTS: Our data indicated that ursodeoxycholic acid is well tolerated by all subjects at all doses. We also showed that ursodeoxycholic acid is well absorbed after oral administration and crosses the blood-brain barrier in a dose-dependent manner. CONCLUSIONS: These results show excellent safety and tolerability of ursodeoxycholic acid. The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis.
Gareth J Parry; Cecilia M P Rodrigues; Marcia M Aranha; Sarah J Hilbert; Cynthia Davey; Praful Kelkar; Walter C Low; Clifford J Steer
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Clinical neuropharmacology     Volume:  33     ISSN:  1537-162X     ISO Abbreviation:  Clin Neuropharmacol     Publication Date:    2010 Jan-Feb
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7607910     Medline TA:  Clin Neuropharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-21     Citation Subset:  IM    
Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55414, USA.
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MeSH Terms
Amyotrophic Lateral Sclerosis / blood,  cerebrospinal fluid*,  drug therapy*
Analysis of Variance
Bile Acids and Salts / blood,  cerebrospinal fluid
Blood-Brain Barrier / drug effects
Cholagogues and Choleretics / adverse effects,  blood,  cerebrospinal fluid*,  pharmacology,  therapeutic use*
Dose-Response Relationship, Drug
Double-Blind Method
Drug Tolerance
Middle Aged
Time Factors
Treatment Outcome
Ursodeoxycholic Acid / adverse effects,  blood,  cerebrospinal fluid*,  pharmacology,  therapeutic use*
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 128-13-2/Ursodeoxycholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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