A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression
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 enro...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Neurology Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/582075 |
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| author | Todd D. Levine Robert Bowser Nicole C. Hank Stephen Gately Dietrich Stephan David S. Saperstein Kendall Van Keuren-Jensen |
| author_facet | Todd D. Levine Robert Bowser Nicole C. Hank Stephen Gately Dietrich Stephan David S. Saperstein Kendall Van Keuren-Jensen |
| author_sort | Todd D. Levine |
| collection | DOAJ |
| description | 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 -.86 (P=.18). 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. |
| format | Article |
| id | doaj-art-d4dbd840fdb04494b0fdee539463b68c |
| institution | Kabale University |
| issn | 2090-1852 2090-1860 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neurology Research International |
| spelling | doaj-art-d4dbd840fdb04494b0fdee539463b68c2025-02-03T06:01:46ZengWileyNeurology Research International2090-18522090-18602012-01-01201210.1155/2012/582075582075A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease ProgressionTodd D. Levine0Robert Bowser1Nicole C. Hank2Stephen Gately3Dietrich Stephan4David S. Saperstein5Kendall Van Keuren-Jensen6Phoenix Neurological Associates, 5090 N 40th Street Suite 250, Phoenix, AZ 85018, USADivision of Neurology, Barrow Neurological Institute, 350 W Thomas Road, Phoenix, AZ 85013, USAPhoenix Neurological Associates, 5090 N 40th Street Suite 250, Phoenix, AZ 85018, USADivision of Neurogenomics, Translational Genomics Research Institute (TGen), 445 N 5th Street, Phoenix, AZ 85004, USASilicon Valley Biosystems, 3000 Sand Hill Road, Menlo Park, CA 94025, USAPhoenix Neurological Associates, 5090 N 40th Street Suite 250, Phoenix, AZ 85018, USADivision of Neurogenomics, Translational Genomics Research Institute (TGen), 445 N 5th Street, Phoenix, AZ 85004, USAObjectives. 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 -.86 (P=.18). 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.http://dx.doi.org/10.1155/2012/582075 |
| spellingShingle | Todd D. Levine Robert Bowser Nicole C. Hank Stephen Gately Dietrich Stephan David S. Saperstein Kendall Van Keuren-Jensen A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression Neurology Research International |
| title | A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression |
| title_full | A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression |
| title_fullStr | A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression |
| title_full_unstemmed | A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression |
| title_short | A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression |
| title_sort | pilot trial of pioglitazone hcl and tretinoin in als cerebrospinal fluid biomarkers to monitor drug efficacy and predict rate of disease progression |
| url | http://dx.doi.org/10.1155/2012/582075 |
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