Pioglitazone / reduction of brain atrophy
Posted: Wed May 09, 2007 4:30 am
Hey,
The brain atrophy impact seems to be a very positive element and very consistent with the previous case-study where PIO was used for a person with progressive MS. Hopefully there will be continuation on this research.
Best Regards,
Degerlache
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Results of a Phase I Trial of Pioglitazone in RRMS Patients
Claudia Kaiser, Dinesh Shukla, Glenn Stebbins, Demetrios Skias, George Katsamakis, Hoffman Estates, IL, Dusan Stefoski, Douglas Jeffery, Winston Salem, NC, Douglas L. Feinstein, Chicago, IL
OBJECTIVE: Based on pre-clinical studies and case reports, we tested if treatment with Actos (Pioglitazone), an agonist of Peroxisome Proliferator Activated Receptor Gamma could provide benefit in RRMS patients. BACKGROUND: The PPARg agonist Actos is FDA-approved for treatment of type 2 diabetes based on its insulin sensitizing effects. However, Actos exerts anti-inflammatory effects in T-cells and glial cells; improves glial metabolism; and is neuroprotective. In mouse models of MS, Actos reduced disease incidence and severity. In view of its good safety profile, we tested the effects of Actos in a small cohort of RRMS patients. DESIGN/METHODS: We carried out a one-year, double-blinded, placebo-controlled Phase I trial of Actos (30 mg daily, p.o.) in RRMS patients taking Avonex. Primary outcomes were safety (liver function, Gd enhancement). Secondary outcomes were FLAIR lesion burden, grey matter atrophy, and MSFC and EDSS. Other analyses included DTI, fMRI, and measurements of serum cytokine levels. Comparisons of group means were done by unpaired two-tailed T-test. RESULTS: Twenty two patients completed the trial. There were no indications of liver toxicity, edema, or increased Gd-enhancing lesions. The average EDSS at baseline was 2.5 1.7 and did not change over 1 year; average MSFC score showed similar improvement in both groups. After 1 year FLAIR lesion volume increased in the placebo group (109 23%, n=9); but decreased in the Actos group (93 12%, n=8). Grey matter atrophy was significantly reduced by Actos (6.5 0.7% versus 3.5 0.9% decrease, P < .05). Analyses of DTI data for effects on white matter integrity, and results of cytokine analyses will be presented. CONCLUSIONS/RELEVANCE: Daily Actos (30 mg p.o.) is tolerated in RRMS patients and there are indications that it may reduce disease progression assessed by FLAIR volume and grey matter atrophy. Further testing in MS patients is therefore warranted. Supported by: Takeda Pharmaceuticals.
Category - MS and Related Diseases
SubCategory - Clinical Science
Tuesday, May 1, 2007 3:15 PM
The brain atrophy impact seems to be a very positive element and very consistent with the previous case-study where PIO was used for a person with progressive MS. Hopefully there will be continuation on this research.
Best Regards,
Degerlache
------------------------------------------------------------------------------------
Results of a Phase I Trial of Pioglitazone in RRMS Patients
Claudia Kaiser, Dinesh Shukla, Glenn Stebbins, Demetrios Skias, George Katsamakis, Hoffman Estates, IL, Dusan Stefoski, Douglas Jeffery, Winston Salem, NC, Douglas L. Feinstein, Chicago, IL
OBJECTIVE: Based on pre-clinical studies and case reports, we tested if treatment with Actos (Pioglitazone), an agonist of Peroxisome Proliferator Activated Receptor Gamma could provide benefit in RRMS patients. BACKGROUND: The PPARg agonist Actos is FDA-approved for treatment of type 2 diabetes based on its insulin sensitizing effects. However, Actos exerts anti-inflammatory effects in T-cells and glial cells; improves glial metabolism; and is neuroprotective. In mouse models of MS, Actos reduced disease incidence and severity. In view of its good safety profile, we tested the effects of Actos in a small cohort of RRMS patients. DESIGN/METHODS: We carried out a one-year, double-blinded, placebo-controlled Phase I trial of Actos (30 mg daily, p.o.) in RRMS patients taking Avonex. Primary outcomes were safety (liver function, Gd enhancement). Secondary outcomes were FLAIR lesion burden, grey matter atrophy, and MSFC and EDSS. Other analyses included DTI, fMRI, and measurements of serum cytokine levels. Comparisons of group means were done by unpaired two-tailed T-test. RESULTS: Twenty two patients completed the trial. There were no indications of liver toxicity, edema, or increased Gd-enhancing lesions. The average EDSS at baseline was 2.5 1.7 and did not change over 1 year; average MSFC score showed similar improvement in both groups. After 1 year FLAIR lesion volume increased in the placebo group (109 23%, n=9); but decreased in the Actos group (93 12%, n=8). Grey matter atrophy was significantly reduced by Actos (6.5 0.7% versus 3.5 0.9% decrease, P < .05). Analyses of DTI data for effects on white matter integrity, and results of cytokine analyses will be presented. CONCLUSIONS/RELEVANCE: Daily Actos (30 mg p.o.) is tolerated in RRMS patients and there are indications that it may reduce disease progression assessed by FLAIR volume and grey matter atrophy. Further testing in MS patients is therefore warranted. Supported by: Takeda Pharmaceuticals.
Category - MS and Related Diseases
SubCategory - Clinical Science
Tuesday, May 1, 2007 3:15 PM