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Neurology Research International
Volume 2012 (2012), Article ID 582075, 6 pages
Clinical Study

A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

1Phoenix Neurological Associates, 5090 N 40th Street Suite 250, Phoenix, AZ 85018, USA
2Division of Neurology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ 85013, USA
3Division of Neurogenomics, Translational Genomics Research Institute (TGen), 445 N 5th Street, Phoenix, AZ 85004, USA
4Silicon Valley Biosystems, 3000 Sand Hill Road, Menlo Park, CA 94025, USA

Received 28 March 2012; Revised 16 May 2012; Accepted 16 May 2012

Academic Editor: Kenneth Hensley

Copyright © 2012 Todd D. Levine et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs) were performed to measure cerebrospinal fluid (CSF) biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of ( ). Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.